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Project Title:  Determination of Risk for and Occurrence of Heart Disease from Space Radiation Reduce
Fiscal Year: FY 2019 
Division: Human Research 
Research Discipline/Element:
HRP SR:Space Radiation
Start Date: 01/08/2015  
End Date: 01/07/2019  
Task Last Updated: 03/19/2019 
Download report in PDF pdf
Principal Investigator/Affiliation:   Baker, John  Ph.D. / Medical College of Wisconsin 
Address:  Congenital Heart Surgery 
8701 W Watertown Plank Rd 
Milwaukee , WI 53226-3548 
Email: jbaker@mcw.edu 
Phone: 414-955-8706  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: Medical College of Wisconsin 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Kronenberg, Amy  D.Sc. Lawrence Berkeley National Laboratory 
Key Personnel Changes / Previous PI: March 2019: There have been no changes to the PI or other key personnel. November 2016: There have been no changes to the PI or other key personnel.
Project Information: Grant/Contract No. NNX15AD69G 
Responsible Center: NASA JSC 
Grant Monitor: Simonsen, Lisa  
Center Contact:  
lisa.c.simonsen@nasa.gov 
Solicitation / Funding Source: 2013-14 HERO NNJ13ZSA002N-RADIATION 
Grant/Contract No.: NNX15AD69G 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) SR:Space Radiation
Human Research Program Risks: (1) Degen:Risk Of Cardiovascular Disease and Other Degenerative Tissue Effects From Radiation Exposure (IRP Rev F)
Human Research Program Gaps: (1) Degen01:How can tissue specific experimental models be developed for the major degenerative tissue risks, including cardiovascular, lens, digestive, endocrine, and other tissue systems in order to estimate space radiation risks for degenerative diseases? (IRP Rev F)
(2) Degen02:What are the adverse outcome pathways associated with degenerative tissues changes in the cardiovascular, cerebrovascular, lens, immune, digestive, endocrine, and other tissue systems? What are the key events or hallmarks, their time sequence, and their associated biomarkers? (IRP Rev J)
(3) Degen03:What are the progression rates and latency periods for radiation-induced degenerative diseases, and how do progression rates depend on age, sex, radiation type, or other physiological or environmental factors? (IRP Rev F)
(4) Degen05:What quantitative procedures or theoretical models are needed to extrapolate molecular, cellular, or animal results to predict degenerative tissue risks in astronauts? How can human epidemiology data best support these procedures or models?
Task Description: The objective of this application is to determine the increased risk of developing degenerative cardiac disease because of exposure to representative components of space radiation. Ground-based animal studies will be used to assess the increased risk for developing degenerative cardiovascular disease. A model of accelerated coronary fibrosis and the degeneration of heart morphology and function following exposure to ionizing radiation, in previously healthy rats, has already been developed and validated. In this rat model, whole body ionizing radiation with a single dose of 10 Gy of X-rays resulted in clinically relevant changes in cardiac function that can be measured, noninvasively. Our central hypothesis is that whole body exposure to space-relevant doses of galactic cosmic rays (GCRs) will increase the risk for developing degenerative cardiovascular disease.

Three Specific Aims are proposed to directly address the issue of cardiovascular risk using experimental approaches in a rat model of disease progression to apply the results from the rat studies to astronauts. The proposed investigations directly address important aspects of the NASA Human Research Program (HRP) Degenerative Tissue Gaps, as set forth in the Human Research Roadmap. HRP gaps are identified that are addressed by each Specific Aim. The proposed research will provide important information to help close these gaps.

Specific Aim 1: Determine the progression rates, latency periods for single beams of iron ions, silicon ions, and protons of risk for and occurrence of degenerative disease in the cardiovascular system resulting from ground-based studies of GCRs. (HRP Gaps Degen-1, -2, and -3).

Specific Aim 2: Determine the progression rates, latency periods for gamma rays of risk for and occurrence of degenerative disease in the cardiovascular system resulting from ground-based studies of gamma radiation so that relative biological effectiveness can be estimated. (HRP Gaps Degen-1, -2, and -3).

Specific Aim 3: Determine the progression rates, latency periods for mixed beams of iron ions, silicon ions, and protons of risk for and occurrence of degenerative disease in the cardiovascular system resulting from ground-based studies of GCRs. (HRP Gaps Degen-1, -2, and -3).

Research Impact/Earth Benefits: This research benefits life on Earth as it relates to patients who receive therapeutic radiation for the treatment of cancer and to individuals who receive accidental exposure to radiation from a nuclear accident.

Task Progress & Bibliography Information FY2019 
Task Progress: FINAL REPORTING MARCH 2019

This project addresses the following goals set forward in the 2014 NASA NRA (NASA Research Announcement) for Radiation Studies: 1) to provide detailed physiological and bio-molecular characterization of degenerative tissue responses to space-like radiation doses that are mission relevant for future human spaceflight outside low Earth orbit and 2) to determine relative biological effectiveness (RBE) values for space radiations in appropriate animals using relevant intermediate as well as late physiological endpoints and effects. These experimentally derived RBE values will be used to provide quantitative inputs into methods and models to calculate degenerative tissue responses in humans following exposures in space. The objective of this application is to determine the increased risk of developing degenerative cardiac disease because of exposure to representative components of space radiation. Ground-based animal studies will be used to assess the increased risk for developing degenerative cardiovascular disease. A model of accelerated coronary fibrosis and the degeneration of heart morphology and function following exposure to ionizing radiation, in previously healthy rats, has already been developed and validated. In this rat model, whole body ionizing radiation with a single dose of 10 Gy of X-rays resulted in clinically relevant changes in cardiac function that can be measured, noninvasively. Our central hypothesis is that whole body exposure to space-relevant doses of galactic cosmic rays (GCRs) will increase the risk for developing degenerative cardiovascular disease.

The central hypothesis of this project is that whole body exposure to space-relevant doses of galactic cosmic rays (GCRs) will increase the risk for developing degenerative cardiovascular disease. Three Specific Aims were proposed to directly address the issue of cardiovascular risk using experimental approaches in a rat model of disease progression to apply the results from the rat studies to astronauts. The proposed investigations directly address important aspects of the NASA Human Research Program (HRP) Degenerative Tissue Gaps, as set forth in the Human Research Roadmap. HRP gaps are identified that are addressed by each Specific Aim. The proposed research will provide important information to help close these gaps.

Specific Aim 1: Determine the progression rates, latency periods for single beams of iron ions, silicon ions, and protons of risk for and occurrence of degenerative disease in the cardiovascular system resulting from ground-based studies of GCRs. (HRP Gaps Degen-1, -2, and -3).

Specific Aim 2: Determine the progression rates, latency periods for gamma rays of risk for and occurrence of degenerative disease in the cardiovascular system resulting from ground-based studies of gamma radiation so that relative biological effectiveness can be estimated. (HRP Gaps Degen-1, -2, and -3).

Specific Aim 3: Determine the progression rates, latency periods for mixed beams of iron ions, silicon ions, and protons of risk for and occurrence of degenerative disease in the cardiovascular system resulting from ground-based studies of GCRs. (HRP Gaps Degen-1, -2, and -3).

Following irradiation of the rats (n=12 per group) we have determined changes in risk factors for cardiovascular disease and cardiac injury in a longitudinal study. The end points measured included total cholesterol and triglycerides in blood, clinically accepted biomarker of risk for cardiovascular disease. These measurements were made monthly over a 9 month follow up period. We performed histological studies and cardiac echocardiography studies to measure injury to the heart at the end of the study. We used this data to determine dose-response relationships for single beams 56Fe, 28Si, and protons and mixed beams of 56Fe, 28Si, and protons as representative ions in GCRs. The relationship between dose for particles (56Fe, 28Si, or protons), compared with gamma-rays as the reference radiation, were determined for changes in risk factors for cardiac disease (cholesterols and triglycerides), cardiovascular injury (radial and circumferential strain using echocardiography), and renal injury (blood urea nitrogen and blood pressure) following whole body irradiation. Dose-response relationships were established for renal disease.

Male Wistar rats were exposed to mixed beams 1 GeV protons (80% of the total dose to each subject), 500 MeV/n Si ions (10% of the total dose to each subject), and 600 MeV/n Fe ions (10% of the total dose to each subject). Our five dose groups were: 0, 0.25 Gy, 0.5 Gy, 0.75 Gy, and 1.5 Gy, dose rate 50 cGy/min. Exposure of rats to 1.5 Gy of simulated GCRs increased perivascular collagen content by 148% compared with sham-irradiated, age-matched controls after 270 days. These findings identify a cardiac vascular pathology resulting from exposure to representative components of GCRs. Irradiation of WAG rats with 0.25 Gy, 0.5 Gy, and 0.75 Gy of mixed field beams showed no increase above baseline levels for perivascular collagen content compared with sham-irradiated, age-matched rats after 270 days. These findings provide evidence of a threshold dose for cardiac fibrosis resulting from exposure to representative components of GCRs.

Total cholesterol and triglyceride levels in sham-irradiated rats progressively increased over the 270-day study period compared with values at 30 days but each was essentially unchanged in gamma-ray exposed rats when compared with age-matched sham-irradiated controls. Coronary vessels and cardiomyocytes from rats exposed to even the highest dose of 6.0 Gy of gamma-rays remained normal in appearance compared with hearts from age-matched, sham-irradiated rats. There was no increase in cardiac perivascular collagen deposition in irradiated hearts compared with age-matched sham-irradiated controls.

Blood urea nitrogen and creatinine levels were largely unchanged in sham-irradiated rats over the 270-day study period, and these levels were also unchanged over the 270 day follow up period for all the gamma-irradiated rats. Cortex and medulla from rats 270 days after exposure to 6.0 Gy of gamma-rays remained normal in appearance compared with kidneys from age-matched, sham-irradiated rats. Systemic blood pressure (systolic and diastolic) was not significantly elevated over the 270-day period following whole body exposure to gamma-rays.

• There have been no deaths associated with any dose of radiation.

• Risk factors for cardiac disease and renal injury were essentially unchanged after exposure of rats to individual beams of protons, 28Si ions, and 56Fe ions over the 270 day follow up period.

• Rats exposed to mixed beams of protons, 28Si ions, and 56Fe ions showed modest changes in risk for cardiac disease and kidney injury after irradiation and increased perivascular collagen deposition at the end of the 270 day follow up period.

• We monitored early changes (30 days and 60 days after irradiation) for the same oxidative and inflammatory biomarkers in rats as those currently being evaluated in astronauts aboard the ISS. Biomarkers of oxidative stress and inflammation increased 30 days after irradiation and decreased 60 days after irradiation with mixed beams.

Our studies are starting to provide an estimation for the occurrence of cardiac disease after exposure to representative components of space radiation that will enable NASA to evaluate permissible exposure limits.

ANNUAL REPORTING NOVEMBER 2018: This project addresses the following goals set forward in the 2014 NASA NRA (NASA Research Announcement) for Radiation Studies: 1) to provide detailed physiological and bio-molecular characterization of degenerative tissue responses to space-like radiation doses that are mission relevant for future human spaceflight outside low Earth orbit and 2) to determine relative biological effectiveness (RBE) values for space radiations in appropriate animals using relevant intermediate as well as late physiological endpoints and effects. These experimentally derived RBE values are to provide quantitative inputs into methods and models to calculate degenerative tissue responses in humans following exposures in space. The central hypothesis of this project is that whole body exposure to space-relevant doses of galactic cosmic rays (GCRs) will increase the risk for developing degenerative cardiovascular disease. Three specific aims are proposed to address the issue of cardiovascular risk using experimental approaches in a rat model and the mathematical modeling of rat and human data relevant to the research questions.

Specific Aim 1: Determine the progression rates, latency periods and relative biological effectiveness (RBE) of iron ions, silicon and protons compared to gamma-rays for degenerative disease in the cardiovascular system resulting from ground-based exposure to GCRs.

Specific Aim 2: Determine the importance of the kidney in the mechanisms underlying cardiac disease from HZE ion exposure.

Specific Aim 3: Develop a theoretical model of disease progression to extrapolate the results for charged particle-induced cardiac risks in rats to degenerative cardiac disease in astronauts.

Following irradiation of the rats (n=12 per group) we are determining changes in risk factors for cardiovascular disease and cardiac injury in a longitudinal study. The end points to be measured include total cholesterol, HDL-cholesterol, and triglycerides in blood. These measurements will be made monthly over a 9 month follow up period. We performed histological studies and cardiac echocardiography studies to measure injury to the heart at the end of the study. We are using this data to determine dose-response relationships for 56Fe, 28Si, and protons as representative ions in GCRs.

Male Wistar rats have been exposed to mixed beams 1 GeV protons (80% of the total dose to each subject), 500 MeV/n Si ions (10% of the total dose to each subject), and 600 MeV/n Fe ions (10% of the total dose to each subject). Our five dose groups were: 0, 0.25 Gy, 0.5 Gy, 0.75 Gy, and 1.5 Gy, dose rate 50 cGy/min.

Significant findings

• There have been no deaths associated with any dose of radiation,

• Risk factors for cardiac disease and renal injury were essentially unchanged after exposure of rats to individual beams of protons, 28Si ions, and 56Fe ions over the 270 day follow up period,

• Rats exposed to mixed beams of protons, 28Si ions, and 56Fe ions showed modest changes in risk for cardiac disease and kidney injury after irradiation and increased perivascular collagen deposition at the end of the 270 day follow up period,

• Biomarkers of oxidative stress and inflammation increased 30 days after irradiation and decreased 60 days after irradiation with mixed beams,

• No increase in risk factors for cardiac disease after exposure to gamma radiation.

Bibliography Type: Description: (Last Updated: 11/05/2021) 

Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings Baker J, Lenarczyk M, Moulder J, Little M, Hopewell J, Kronenberg A. "Determination of risk for and occurrence of heart disease from space radiation." 2018 NASA Human Research Program Investigators’ Workshop, Galveston, TX, January 22-25, 2018.

2018 NASA Human Research Program Investigators’ Workshop, Galveston, TX, January 22-25, 2018. , Jan-2018

Abstracts for Journals and Proceedings Kronenberg A, Gauny S, Turker M, Raber PJ, Grygoryev D, Baker J, Lenarczyk M, Mader M, Torres ER. "Biological effects of rapid sequential exposure to multiple ion beams in mammalian model systems: cancer-relevant and non-cancer endpoints." Presented at Committee on Space Research (COSPAR) 2018 42nd Scientific Assembly, Pasadena, CA, July 14-22, 2018.

Committee on Space Research (COSPAR) 2018 42nd Scientific Assembly, Pasadena, CA, July 14-22, 2018. , Jul-2018

Abstracts for Journals and Proceedings Baker J, Lenarczyk M, Moulder J, Little M, Hopewell J, Kronenberg A. "Determination of risk for and occurrence of heart disease from space radiation." 2019 NASA Human Research Program Investigators’ Workshop, Galveston, TX, January 22-25, 2019.

2019 NASA Human Research Program Investigators’ Workshop, Galveston, TX, January 22-25, 2019. , Jan-2019

Articles in Peer-reviewed Journals Lenarczyk M, Kronenberg A, Mader M, North PE, Komorowski R, Cheng Q, Little MP, Chiang IH, LaTessa C, Jardine J, Baker JE. "Age at exposure to radiation determines severity of renal and cardiac disease in rats." Radiat Res. 2019 Jul;192(1):63-74. Epub 2019 May 16. https://doi.org/10.1667/RR15043.1 ; PubMed PMID: 31095446 , Jul-2019
Articles in Peer-reviewed Journals Malik M, Suboc TM, Tyagi S, Salzman N, Wang J, Ying R, Tanner MJ, Kakarla M, Baker JE, Widlansky ME. "Lactobacillus plantarum 299v supplementation improves vascular endothelial function and reduces inflammatory biomarkers in men with stable coronary artery disease." Circ Res. 2018 Oct 12;123(9):1091-102. https://doi.org/10.1161/CIRCRESAHA.118.313565 ; PubMed PMID: 30355158 ; PubMed Central PMCID: PMC6205737 , Oct-2018
Project Title:  Determination of Risk for and Occurrence of Heart Disease from Space Radiation Reduce
Fiscal Year: FY 2018 
Division: Human Research 
Research Discipline/Element:
HRP SR:Space Radiation
Start Date: 01/08/2015  
End Date: 01/07/2019  
Task Last Updated: 11/09/2017 
Download report in PDF pdf
Principal Investigator/Affiliation:   Baker, John  Ph.D. / Medical College of Wisconsin 
Address:  Congenital Heart Surgery 
8701 W Watertown Plank Rd 
Milwaukee , WI 53226-3548 
Email: jbaker@mcw.edu 
Phone: 414-955-8706  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: Medical College of Wisconsin 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Kronenberg, Amy  D.Sc. Lawrence Berkeley National Laboratory 
Key Personnel Changes / Previous PI: November 2016: There have been no changes to the PI or other key personnel.
Project Information: Grant/Contract No. NNX15AD69G 
Responsible Center: NASA JSC 
Grant Monitor: Simonsen, Lisa  
Center Contact:  
lisa.c.simonsen@nasa.gov 
Solicitation / Funding Source: 2013-14 HERO NNJ13ZSA002N-RADIATION 
Grant/Contract No.: NNX15AD69G 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) SR:Space Radiation
Human Research Program Risks: (1) Degen:Risk Of Cardiovascular Disease and Other Degenerative Tissue Effects From Radiation Exposure (IRP Rev F)
Human Research Program Gaps: (1) Degen01:How can tissue specific experimental models be developed for the major degenerative tissue risks, including cardiovascular, lens, digestive, endocrine, and other tissue systems in order to estimate space radiation risks for degenerative diseases? (IRP Rev F)
(2) Degen02:What are the adverse outcome pathways associated with degenerative tissues changes in the cardiovascular, cerebrovascular, lens, immune, digestive, endocrine, and other tissue systems? What are the key events or hallmarks, their time sequence, and their associated biomarkers? (IRP Rev J)
(3) Degen03:What are the progression rates and latency periods for radiation-induced degenerative diseases, and how do progression rates depend on age, sex, radiation type, or other physiological or environmental factors? (IRP Rev F)
(4) Degen05:What quantitative procedures or theoretical models are needed to extrapolate molecular, cellular, or animal results to predict degenerative tissue risks in astronauts? How can human epidemiology data best support these procedures or models?
Task Description: The objective of this application is to determine the increased risk of developing degenerative cardiac disease as a result of exposure to representative components of space radiation. Ground-based animal studies will be used to assess the increased risk for developing degenerative cardiovascular disease. A model of accelerated coronary fibrosis and the degeneration of heart morphology and function following exposure to ionizing radiation, in previously healthy rats, has already been developed and validated. In this rat model, whole body ionizing radiation with single doses of 6-10 Gy of X-rays resulted in clinically relevant changes in cardiac function that can be measured, noninvasively. Our central hypothesis is that whole body exposure to space-relevant doses of solar particle event (SPE) protons and galactic cosmic rays (GCRs) will increase the risk for developing degenerative cardiovascular disease.

Three Specific Aims are proposed to directly address the issue of cardiovascular risk using experimental approaches in a rat model and theoretical modeling of disease progression to apply the results from the rat studies to astronauts. The proposed investigations directly address important aspects of the NASA Human Research Program (HRP) Degenerative Tissue Gaps, as set forth in the Human Research Roadmap. HRP gaps are identified that are addressed by each Specific Aim. The proposed research will provide important information to help close these gaps.

Specific Aim 1: Determine the progression rates, latency periods, and relative biological effectiveness (RBE) of iron ions, silicon, and protons compared with gamma rays of risk for and occurrence of degenerative disease in the cardiovascular system resulting from ground-based exposure to GCRs and SPEs. (HRP Gaps Degen-1, -2, and -3).

Specific Aim 2: Determine the importance of the kidney in the mechanisms underlying cardiac disease from HZE (high energy particles) ion exposure. (HRP Gaps Degen-1, -2, and -3).

Specific Aim 3: Develop a theoretical model of disease progression to extrapolate results on charged particle-induced cardiac risks in rats to degenerative cardiac disease in astronauts. (HRP Gaps Degen-1, -5).

Research Impact/Earth Benefits: This research benefits life on Earth as it relates to patients who receive therapeutic radiation for the treatment of cancer and to individuals who receive accidental exposure to radiation from a nuclear accident.

Task Progress & Bibliography Information FY2018 
Task Progress: This project addresses the following goals set forward in the 2014 NASA NRA for Radiation Studies: 1) to provide detailed physiological and bio-molecular characterization of degenerative tissue responses to space-like radiation doses that are mission relevant for future human spaceflight outside low Earth orbit and 2) to determine relative biological effectiveness (RBE) values for space radiations in appropriate animals using relevant intermediate as well as late physiological endpoints and effects. These experimentally derived RBE values to provide quantitative inputs into methods and models to calculate degenerative tissue responses in humans following exposures in space. The central hypothesis of this project is that whole body exposure to space-relevant doses of galactic cosmic rays (GCRs) will increase the risk for developing degenerative cardiovascular disease. Three specific aims are proposed to address the issue of cardiovascular risk using experimental approaches in a rat model and the mathematical modeling of rat and human data relevant to the research questions.

Specific Aim 1: Determine the progression rates, latency periods and relative biological effectiveness (RBE) of iron ions, silicon and protons compared to gamma-rays for degenerative disease in the cardiovascular system resulting from ground-based exposure to GCRs.

Specific Aim 2: Determine the importance of the kidney in the mechanisms underlying cardiac disease from HZE ion exposure.

Specific Aim 3: Develop a theoretical model of disease progression to extrapolate the results for charged particle-induced cardiac risks in rats to degenerative cardiac disease in astronauts.

Following irradiation of the rats (n=12 per group) we are determining changes in risk factors for cardiovascular disease and cardiac injury in a longitudinal study. The end points to be measured include total cholesterol, HDL-cholesterol, and triglycerides in blood. These measurements will be made monthly over a 9 month follow up period. We will perform histological studies and cardiac echocardiography studies to measure injury to the heart at the end of the study. We will use this data to determine dose-response relationships for 56Fe, 28Si, and protons as representative ions in GCRs.

Male Wistar rats, 6 months of age, have been exposed to 4 doses of 600 MeV/n 56Fe (LET = 174 keV/µm); 0.1, 0.25, 0.5, or 1.0 Gy, 4 doses of 1000 MeV protons (LET = 0.24 keV/µm); 0.25, 0.5, 1.0, or 1.5 Gy, 4 doses of 500 MeV/n 28Si (LET = 54 keV/µm); 0.25, 0.50, 0.75, and 1.5 Gy, and 3 doses of 137Cs; 1.5, 3.0, and 6.0 Gy. Sham-irradiated rats served as controls. Twelve rats were included in each experimental group. There have been no deaths associated with any dose of radiation.

Risk factors for cardiac disease (total cholesterol and triglycerides) were unchanged over the 270 day follow period for 56Fe, protons, and 137Cs. Risk factors for cardiac disease were elevated at 30 days after irradiation with 0.25 and 0.50 Gy 28Si compared with age-matched sham-irradiated controls. There were no changes in these risk factors for rats irradiated with 28Si from 90 to 270 days.

Kidney injury (blood urea nitrogen and blood pressure) was not elevated over the 270 day follow period for 56Fe, protons, and 137Cs. Blood urea nitrogen was elevated at 30 days after irradiation with 0.25, 0.50, 0.75, and 1.5 Gy 28Si compared with age-matched sham-irradiated controls. There were no changes in blood urea nitrogen for rats irradiated with 28Si from 60 to 270 days.

Bibliography Type: Description: (Last Updated: 11/05/2021) 

Show Cumulative Bibliography Listing
 
 None in FY 2018
Project Title:  Determination of Risk for and Occurrence of Heart Disease from Space Radiation Reduce
Fiscal Year: FY 2017 
Division: Human Research 
Research Discipline/Element:
HRP SR:Space Radiation
Start Date: 01/08/2015  
End Date: 01/07/2019  
Task Last Updated: 11/28/2016 
Download report in PDF pdf
Principal Investigator/Affiliation:   Baker, John  Ph.D. / Medical College of Wisconsin 
Address:  Congenital Heart Surgery 
8701 W Watertown Plank Rd 
Milwaukee , WI 53226-3548 
Email: jbaker@mcw.edu 
Phone: 414-955-8706  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: Medical College of Wisconsin 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Kronenberg, Amy  D.Sc. Lawrence Berkeley National Laboratory 
Key Personnel Changes / Previous PI: November 2016: There have been no changes to the PI or other key personnel.
Project Information: Grant/Contract No. NNX15AD69G 
Responsible Center: NASA JSC 
Grant Monitor: Simonsen, Lisa  
Center Contact:  
lisa.c.simonsen@nasa.gov 
Solicitation / Funding Source: 2013-14 HERO NNJ13ZSA002N-RADIATION 
Grant/Contract No.: NNX15AD69G 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) SR:Space Radiation
Human Research Program Risks: (1) Degen:Risk Of Cardiovascular Disease and Other Degenerative Tissue Effects From Radiation Exposure (IRP Rev F)
Human Research Program Gaps: (1) Degen01:How can tissue specific experimental models be developed for the major degenerative tissue risks, including cardiovascular, lens, digestive, endocrine, and other tissue systems in order to estimate space radiation risks for degenerative diseases? (IRP Rev F)
(2) Degen02:What are the adverse outcome pathways associated with degenerative tissues changes in the cardiovascular, cerebrovascular, lens, immune, digestive, endocrine, and other tissue systems? What are the key events or hallmarks, their time sequence, and their associated biomarkers? (IRP Rev J)
(3) Degen03:What are the progression rates and latency periods for radiation-induced degenerative diseases, and how do progression rates depend on age, sex, radiation type, or other physiological or environmental factors? (IRP Rev F)
(4) Degen05:What quantitative procedures or theoretical models are needed to extrapolate molecular, cellular, or animal results to predict degenerative tissue risks in astronauts? How can human epidemiology data best support these procedures or models?
Task Description: The objective of this application is to determine the increased risk of developing degenerative cardiac disease as a result of exposure to representative components of space radiation. Ground-based animal studies will be used to assess the increased risk for developing degenerative cardiovascular disease. A model of accelerated coronary fibrosis and the degeneration of heart morphology and function following exposure to ionizing radiation, in previously healthy rats, has already been developed and validated. In this rat model, whole body ionizing radiation with single doses of 6-10 Gy of X-rays resulted in clinically relevant changes in cardiac function that can be measured, noninvasively. Our central hypothesis is that whole body exposure to space-relevant doses of solar particle event (SPE) protons and galactic cosmic rays (GCRs) will increase the risk for developing degenerative cardiovascular disease.

Three Specific Aims are proposed to directly address the issue of cardiovascular risk using experimental approaches in a rat model and theoretical modeling of disease progression to apply the results from the rat studies to astronauts. The proposed investigations directly address important aspects of the NASA Human Research Program (HRP) Degenerative Tissue Gaps, as set forth in the Human Research Roadmap. HRP gaps are identified that are addressed by each Specific Aim. The proposed research will provide important information to help close these gaps.

Specific Aim 1: Determine the progression rates, latency periods, and relative biological effectiveness (RBE) of iron ions, silicon, and protons compared with gamma rays of risk for and occurrence of degenerative disease in the cardiovascular system resulting from ground-based exposure to GCRs and SPEs. (HRP Gaps Degen-1, -2, and -3).

Specific Aim 2: Determine the importance of the kidney in the mechanisms underlying cardiac disease from HZE (high energy particles) ion exposure. (HRP Gaps Degen-1, -2, and -3).

Specific Aim 3: Develop a theoretical model of disease progression to extrapolate results on charged particle-induced cardiac risks in rats to degenerative cardiac disease in astronauts. (HRP Gaps Degen-1, -5).

Research Impact/Earth Benefits: This research benefits life on Earth as it relates to patients who receive therapeutic radiation for the treatment of cancer and to individuals who receive accidental exposure to radiation from a nuclear accident.

Task Progress & Bibliography Information FY2017 
Task Progress: This project addresses the following goals set forward in the 2014 NASA Research Announcement (NRA) for Radiation Studies: 1) to provide detailed physiological and bio-molecular characterization of degenerative tissue responses to space-like radiation doses that are mission relevant for future human spaceflight outside low Earth orbit and 2) to determine relative biological effectiveness (RBE) values for space radiations in appropriate animals using relevant intermediate as well as late physiological endpoints and effects. These experimentally derived RBE values to provide quantitative inputs into methods and models to calculate degenerative tissue responses in humans following exposures in space. The central hypothesis of this project is that whole body exposure to space-relevant doses of galactic cosmic rays (GCRs) will increase the risk for developing degenerative cardiovascular disease. Three specific aims are proposed to address the issue of cardiovascular risk using experimental approaches in a rat model and the mathematical modeling of rat and human data relevant to the research questions.

Specific Aim 1: Determine the progression rates, latency periods and relative biological effectiveness (RBE) of iron ions, silicon and protons compared to gamma-rays for degenerative disease in the cardiovascular system resulting from ground-based exposure to GCRs.

Specific Aim 2: Determine the importance of the kidney in the mechanisms underlying cardiac disease from HZE ion exposure.

Specific Aim 3: Develop a theoretical model of disease progression to extrapolate the results for charged particle-induced cardiac risks in rats to degenerative cardiac disease in astronauts.

Following irradiation of the rats (n=12 per group) we are determining changes in risk factors for cardiovascular disease and cardiac injury in a longitudinal study. The end points to be measured include total cholesterol, HDL-cholesterol, and triglycerides in blood. These measurements will be made monthly over a 9 month follow up period. We will perform histological studies and cardiac echocardiography studies to measure injury to the heart at the end of the study. We will use this data to determine dose-response relationships for 56Fe, 28Si, and protons as representative ions in GCRs.

Male Wistar rats, 6 months of age, have been exposed to 4 doses of 600 MeV/n 56Fe (LET = 174 keV/µm); 0.1, 0.25, 0.5, or 1.0 Gy, 4 doses of 1000 MeV protons (LET = 0.24 keV/µm); 0.25, 0.5, 1.0, or 1.5 Gy, 4 doses of 500 MeV/n 28Si (LET = 54 keV/µm); 0.25, 0.50, 0.75, and 1.5 Gy, and 3 doses of 137Cs; 1.5, 3.0, and 6.0 Gy. Sham-irradiated rats served as controls. Twelve rats were included in each experimental group. There have been no deaths associated with any dose of radiation.

Risk factors for cardiac disease (total cholesterol and triglycerides) were unchanged over the 270 day follow period for 56Fe, protons, and 137Cs. Risk factors for cardiac disease were elevated at 30 days after irradiation with 0.25 and 0.50 Gy 28Si compared with age-matched sham-irradiated controls. There were no changes in these risk factors for rats irradiated with 28Si from 60 to 150 days.

Kidney injury (blood urea nitrogen and blood pressure) was not elevated over the 270 day follow period for 56Fe, protons, and 137Cs. Blood urea nitrogen was elevated at 30 days after irradiation with 0.25, 0.50, 0.75, and 1.5 Gy 28Si compared with age-matched sham-irradiated controls. There were no changes in blood urea nitrogen for rats irradiated with 28Si from 60 to 150 days.

Bibliography Type: Description: (Last Updated: 11/05/2021) 

Show Cumulative Bibliography Listing
 
 None in FY 2017
Project Title:  Determination of Risk for and Occurrence of Heart Disease from Space Radiation Reduce
Fiscal Year: FY 2016 
Division: Human Research 
Research Discipline/Element:
HRP SR:Space Radiation
Start Date: 01/08/2015  
End Date: 01/07/2019  
Task Last Updated: 11/11/2015 
Download report in PDF pdf
Principal Investigator/Affiliation:   Baker, John  Ph.D. / Medical College of Wisconsin 
Address:  Congenital Heart Surgery 
8701 W Watertown Plank Rd 
Milwaukee , WI 53226-3548 
Email: jbaker@mcw.edu 
Phone: 414-955-8706  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: Medical College of Wisconsin 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Kronenberg, Amy  D.Sc. Lawrence Berkeley National Laboratory 
Key Personnel Changes / Previous PI: November 2015: There have been no changes to the PI or other key personnel.
Project Information: Grant/Contract No. NNX15AD69G 
Responsible Center: NASA JSC 
Grant Monitor: Simonsen, Lisa  
Center Contact:  
lisa.c.simonsen@nasa.gov 
Solicitation / Funding Source: 2013-14 HERO NNJ13ZSA002N-RADIATION 
Grant/Contract No.: NNX15AD69G 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) SR:Space Radiation
Human Research Program Risks: (1) Degen:Risk Of Cardiovascular Disease and Other Degenerative Tissue Effects From Radiation Exposure (IRP Rev F)
Human Research Program Gaps: (1) Degen01:How can tissue specific experimental models be developed for the major degenerative tissue risks, including cardiovascular, lens, digestive, endocrine, and other tissue systems in order to estimate space radiation risks for degenerative diseases? (IRP Rev F)
(2) Degen02:What are the adverse outcome pathways associated with degenerative tissues changes in the cardiovascular, cerebrovascular, lens, immune, digestive, endocrine, and other tissue systems? What are the key events or hallmarks, their time sequence, and their associated biomarkers? (IRP Rev J)
(3) Degen03:What are the progression rates and latency periods for radiation-induced degenerative diseases, and how do progression rates depend on age, sex, radiation type, or other physiological or environmental factors? (IRP Rev F)
(4) Degen05:What quantitative procedures or theoretical models are needed to extrapolate molecular, cellular, or animal results to predict degenerative tissue risks in astronauts? How can human epidemiology data best support these procedures or models?
Task Description: The objective of this application is to determine the increased risk of developing degenerative cardiac disease as a result of exposure to representative components of space radiation. Ground-based animal studies will be used to assess the increased risk for developing degenerative cardiovascular disease. A model of accelerated coronary fibrosis and the degeneration of heart morphology and function following exposure to ionizing radiation, in previously healthy rats, has already been developed and validated. In this rat model, whole body ionizing radiation with single doses of 6-10 Gy of X-rays resulted in clinically relevant changes in cardiac function that can be measured, noninvasively. Our central hypothesis is that whole body exposure to space-relevant doses of solar particle event (SPE) protons and galactic cosmic rays (GCRs) will increase the risk for developing degenerative cardiovascular disease.

Two Specific Aims are proposed to directly address the issue of cardiovascular risk using experimental approaches in a rat model and theoretical modeling of disease progression to apply the results from the rat studies to astronauts. The proposed investigations directly address important aspects of the NASA Human Research Program (HRP) Degenerative Tissue Gaps, as set forth in the Human Research Roadmap. HRP gaps are identified that are addressed by each Specific Aim. The proposed research will provide important information to help close these gaps.

Specific Aim 1: Determine the progression rates, latency periods, and relative biological effectiveness (RBE) of iron ions, silicon, and protons compared with gamma rays of risk for and occurrence of degenerative disease in the cardiovascular system resulting from ground-based exposure to GCRs and SPEs. (HRP Gaps Degen-1, -2, and -3).

Specific Aim 2: Develop a theoretical model of disease progression to extrapolate results on charged particle-induced cardiac risks in rats to degenerative cardiac disease in astronauts. (HRP Gaps Degen-1, -5).

Research Impact/Earth Benefits: This research benefits life on Earth as it relates to patients who receive therapeutic radiation for the treatment of cancer and to individuals who receive accidental exposure to radiation from a nuclear accident.

Task Progress & Bibliography Information FY2016 
Task Progress: This project addresses the following goals set forward in the 2014 NASA Research Announcement (NRA) for Radiation Studies: 1) to provide detailed physiological and bio-molecular characterization of degenerative tissue responses to space-like radiation doses that are mission relevant for future human spaceflight outside low earth orbit and 2) to determine relative biological effectiveness (RBE) values for space radiations in appropriate animals using relevant intermediate as well as late physiological endpoints and effects. These experimentally derived RBE values provide quantitative inputs into methods and models to calculate degenerative tissue responses in humans following exposures in space. The central hypothesis of this project is that whole body exposure to space-relevant doses of galactic cosmic rays (GCRs) will increase the risk for developing degenerative cardiovascular disease. Three specific aims are proposed to address the issue of cardiovascular risk using experimental approaches in a rat model and the mathematical modeling of rat and human data relevant to the research questions.

Specific Aim 1a: Determine the progression rates, latency periods, and relative biological effectiveness (RBE) of iron ions, silicon, and protons compared to gamma-rays for degenerative disease in the cardiovascular system resulting from ground-based exposure to GCRs.

Specific Aim 1b: Determine the importance of the kidney in the mechanisms underlying cardiac disease from HZE ion exposure.

Specific Aim 2: Develop a theoretical model of disease progression to extrapolate the results for charged particle-induced cardiac risks in rats to degenerative cardiac disease in astronauts.

Following irradiation of the rats (n=12 per group) we are determining changes in risk factors for cardiovascular disease and cardiac injury in a longitudinal study. The end points to be measured include total cholesterol, HDL-cholesterol, and triglycerides in blood. These measurements will be made monthly over a 9 month follow up period. We will perform histological studies and cardiac echocardiography studies to measure injury to the heart at the end of the study. We will use this data to determine dose-response relationships for 56Fe, 28Si, and protons as representative ions in GCRs. The relationship between dose for particles (56Fe, 28Si, or protons), compared with gamma-rays as the reference radiation, will be determined for changes in risk factors for cardiac disease (cholesterols and triglycerides), cardiovascular injury (radial and circumferential strain using echocardiography), and renal injury (blood pressure) following whole body irradiation. Dose-response relationships will be established for renal disease.

We are determining the relative biological effectiveness of particles under investigation (56Fe, 28Si, or protons) for a specific risk factor for cardiovascular disease (e.g., the incidence of animals showing a greater than 80 mg/dl increase in total cholesterol levels as an end point). Relative biological effectiveness for other risk factors for cardiovascular, renal, and hepatic disease will also be determined.

Male Wistar rats at 6 months of age have been exposed to 56Fe, protons, and gamma-rays. Our findings at 4 months after irradiation for 56Fe indicate that risk factors for cardiovascular disease are increasing compared with non-irradiated rats at the same age. These rats need be studied over a 9 month period as proposed in the grant to determine their overall response to space radiation.

Bibliography Type: Description: (Last Updated: 11/05/2021) 

Show Cumulative Bibliography Listing
 
 None in FY 2016
Project Title:  Determination of Risk for and Occurrence of Heart Disease from Space Radiation Reduce
Fiscal Year: FY 2015 
Division: Human Research 
Research Discipline/Element:
HRP SR:Space Radiation
Start Date: 01/08/2015  
End Date: 01/07/2019  
Task Last Updated: 02/27/2015 
Download report in PDF pdf
Principal Investigator/Affiliation:   Baker, John  Ph.D. / Medical College of Wisconsin 
Address:  Congenital Heart Surgery 
8701 W Watertown Plank Rd 
Milwaukee , WI 53226-3548 
Email: jbaker@mcw.edu 
Phone: 414-955-8706  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: Medical College of Wisconsin 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Kronenberg, Amy  D.Sc. Lawrence Berkeley National Laboratory 
Project Information: Grant/Contract No. NNX15AD69G 
Responsible Center: NASA JSC 
Grant Monitor: Simonsen, Lisa  
Center Contact:  
lisa.c.simonsen@nasa.gov 
Solicitation / Funding Source: 2013-14 HERO NNJ13ZSA002N-RADIATION 
Grant/Contract No.: NNX15AD69G 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:  
No. of PhD Candidates:  
No. of Master's Candidates:  
No. of Bachelor's Candidates:  
No. of PhD Degrees:  
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Human Research Program Elements: (1) SR:Space Radiation
Human Research Program Risks: (1) Degen:Risk Of Cardiovascular Disease and Other Degenerative Tissue Effects From Radiation Exposure (IRP Rev F)
Human Research Program Gaps: (1) Degen01:How can tissue specific experimental models be developed for the major degenerative tissue risks, including cardiovascular, lens, digestive, endocrine, and other tissue systems in order to estimate space radiation risks for degenerative diseases? (IRP Rev F)
(2) Degen02:What are the adverse outcome pathways associated with degenerative tissues changes in the cardiovascular, cerebrovascular, lens, immune, digestive, endocrine, and other tissue systems? What are the key events or hallmarks, their time sequence, and their associated biomarkers? (IRP Rev J)
(3) Degen03:What are the progression rates and latency periods for radiation-induced degenerative diseases, and how do progression rates depend on age, sex, radiation type, or other physiological or environmental factors? (IRP Rev F)
(4) Degen05:What quantitative procedures or theoretical models are needed to extrapolate molecular, cellular, or animal results to predict degenerative tissue risks in astronauts? How can human epidemiology data best support these procedures or models?
Task Description: The objective of this application is to determine the increased risk of developing degenerative cardiac disease as a result of exposure to representative components of space radiation. Ground-based animal studies will be used to assess the increased risk for developing degenerative cardiovascular disease. A model of accelerated coronary fibrosis and the degeneration of heart morphology and function following exposure to ionizing radiation, in previously healthy rats, has already been developed and validated. In this rat model, whole body ionizing radiation with single doses of 6-10 Gy of X-rays resulted in clinically-relevant changes in cardiac function that can be measured, noninvasively. Our central hypothesis is that whole body exposure to space-relevant doses of solar particle event (SPE) protons and galactic cosmic rays (GCRs) will increase the risk for developing degenerative cardiovascular disease.

Two Specific Aims are proposed to directly address the issue of cardiovascular risk using experimental approaches in a rat model and theoretical modeling of disease progression to apply the results from the rat studies to astronauts. The proposed investigations directly address important aspects of the NASA Human Research Program (HRP) Degenerative Tissue Gaps, as set forth in the Human Research Roadmap. HRP gaps are identified that are addressed by each Specific Aim. The proposed research will provide important information to help close these gaps.

Specific Aim 1: Determine the progression rates, latency periods, and relative biological effectiveness (RBE) of iron ions, silicon, and protons compared with gamma rays of risk for and occurrence of degenerative disease in the cardiovascular system resulting from ground-based exposure to GCRs and SPEs. (HRP Gaps Degen-1, -2 and -3).

Specific Aim 2: Develop a theoretical model of disease progression to extrapolate results on charged particle-induced cardiac risks in rats to degenerative cardiac disease in astronauts. (HRP Gaps Degen-1, -5).

Research Impact/Earth Benefits: 0

Task Progress & Bibliography Information FY2015 
Task Progress: New project for FY2015.

Bibliography Type: Description: (Last Updated: 11/05/2021) 

Show Cumulative Bibliography Listing
 
 None in FY 2015