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Project Title:  Defining the Relation Between Biomarkers of Oxidative and Inflammatory Stress and Atherosclerosis Risk in Astronauts During and After Long-Duration Spaceflight (PI=Lee) Reduce
Images: icon  Fiscal Year: FY 2022 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 03/01/2016  
End Date: 08/31/2023  
Task Last Updated: 01/27/2022 
Download report in PDF pdf
Principal Investigator/Affiliation:   Lee, Stuart M.C. Ph.D. / KBR/NASA Johnson Space Center 
Address:  2400 NASA Parkway 
 
Houston , TX 77058-2749 
Email: stuart.lee-1@nasa.gov 
Phone: 281-483-3726  
Congressional District: 36 
Web:  
Organization Type: NASA CENTER 
Organization Name: KBR/NASA Johnson Space Center 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Smith, Scott  Ph.D. NASA Johnson Space Center 
Feiveson, Alan  Ph.D. Collaborator: NASA Johnson Space Center 
Stenger, Michael  NASA Johnson Space Center 
Laurie, Steven  Ph.D. KBR/NASA Johnson Space Center 
Key Personnel Changes / Previous PI: August 2019 report: Steven Laurie, Ph.D. is CoInvestigator. January 2017: Remove Dr. Rob Ploutz-Snyder as CoInvestigator; Add: Dr. Alan Feiveson as Collaborator.
Project Information: Grant/Contract No. Internal Project 
Responsible Center: NASA JSC 
Grant Monitor: Stenger, Michael  
Center Contact: 281-483-1311 
michael.b.stenger@nasa.gov 
Solicitation / Funding Source: 2010 Crew Health NNJ10ZSA003N 
Grant/Contract No.: Internal Project 
Project Type: FLIGHT 
Flight Program: ISS 
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) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Cardiovascular:Risk of Cardiovascular Adaptations Contributing to Adverse Mission Performance and Health Outcomes (IRP Rev M)
Human Research Program Gaps: (1) CVD-101:To determine whether long-duration weightlessness induces cardiovascular structural and functional changes and/or oxidative stress & damage (OSaD)/inflammation, that can contribute to development of disease (IRP Rev L)
(2) CVD-103:To determine whether the combined effects of relevant deep-space radiation and weightlessness induce additive or synergistic effects on the cardiovascular system, and whether it is of concern for development of disease (IRP Rev L)
Flight Assignment/Project Notes: ISS

NOTE: End date changed to 8/31/2023 per HRP HHC element (Ed., 8/12/21)

Task Description: NOTE: Continuation of "Defining the Relation Between Biomarkers of Oxidative and Inflammatory Stress and Atherosclerosis Risk in Astronauts During and After Long-Duration Spaceflight" ; previous Principal Investigator was Dr. Steven Platts, until March 2016.

Atherosclerosis is the major contributor to cardiovascular disease-related morbidity and mortality. Research indicates that many of the risk factors commonly associated with atherosclerosis contribute to endothelial dysfunction, a process which presents early in life before angiographic evidence of disease and precedes the clinical manifestation of many cardiovascular disease-related disorders. In an effort to compensate for the initial risk factor-related disruptions to homeostasis, there is a compensatory upregulation of atheroprotective mechanisms. However, in the absence of appropriate risk factor management, these defense mechanisms may become overwhelmed and less able to reestablish normal function. Key systems that help maintain vascular homeostasis and are susceptible to differential deleterious alterations include those that help balance levels of oxidative and inflammatory stress. New evidence suggests that long-duration spaceflight may promote oxidative and inflammatory stress through mechanisms such as radiation exposure, diet, physical inactivity, and psychological stress. However, there are no data supporting a causal link between biomarkers of oxidative and inflammatory stress and indices of vascular endothelial dysfunction in spaceflight. As such, we proposed to examine the relation between biomarkers of oxidative and inflammatory stress and well-established measures of vascular endothelial dysfunction (flow mediated dilation (FMD)) and carotid intima-media thickness (cIMT) in astronauts before, during, and after long duration spaceflight.

Research Impact/Earth Benefits: It is well known that inflammation is a key contributor to the development of atherosclerosis. There is also emerging work showing the link with oxidative damage. This work may contribute to general clinical science by showing the interactions of multiple stressors in a unique environment (spaceflight).

Task Progress & Bibliography Information FY2022 
Task Progress: All pre-, in-, and immediate postflight data have been collected and analyzed. A manuscript describing these results has been published (Lee SMC et al. Arterial structure and function during and after long-duration spaceflight. J Appl Physiol 129: 108-123, 2020), and a response (Lee SMC et al. Reply to Greaves et al. J Appl Physiol 129: 113, 2020) to a “Letter to the Editor” (Greaves DK, Robertson AD, Patterson CA, Au JS, Hughson RL. Evidence for increased cardiovascular risk to crew during long duration space missions. J Appl Physiol 129: 1111–1112, 2020) regarding this manuscript also was published. [Ed. Note: See Cumulative Bibliography for these references.] Additionally, the investigators continue to participate in the annual NASA Human Research Program Investigators’ Workshop.

Most astronauts continue to participate in postflight data collections, scheduled to extend to 5 years after landing, although a few are not readily available due to retirement from the astronaut corps or limited travel opportunities coming from international partner organizations, and two have discontinued participation. Thus, we expect that a total of 10 subjects will participate in data collection through 5 years after landing. To date, 8 astronauts have completed data collection through 5 years after landing, and 10 astronauts have completed their 3-year postflight test. Results from this study and previous reports have been used to inform the design of the NASA Standard Measures Study as well the NASA Human System Risk Board-defined risk, “Risk of Cardiovascular Adaptations Contributing to Adverse Mission Performance and Health Outcomes”.

Bibliography Type: Description: (Last Updated: 03/21/2022) 

Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings Lee S, Ribeiro C, Martin D, Smith S, Zwart S, Laurie S, Macias B, Stenger M. "Indices of cardiovascular disease risk in astronauts after long-duration spaceflight in low Earth orbit. " 2022 NASA Human Research Program Investigators’ Workshop, Virtual, February 7-10, 2022.

Abstracts. 2022 NASA Human Research Program Investigators’ Workshop, Virtual, February 7-10, 2022 (Abstract #1133-000499). , Feb-2022

Project Title:  Defining the Relation Between Biomarkers of Oxidative and Inflammatory Stress and Atherosclerosis Risk in Astronauts During and After Long-Duration Spaceflight (PI=Lee) Reduce
Images: icon  Fiscal Year: FY 2021 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 03/01/2016  
End Date: 08/31/2023  
Task Last Updated: 02/17/2021 
Download report in PDF pdf
Principal Investigator/Affiliation:   Lee, Stuart M.C. Ph.D. / KBR/NASA Johnson Space Center 
Address:  2400 NASA Parkway 
 
Houston , TX 77058-2749 
Email: stuart.lee-1@nasa.gov 
Phone: 281-483-3726  
Congressional District: 36 
Web:  
Organization Type: NASA CENTER 
Organization Name: KBR/NASA Johnson Space Center 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Smith, Scott  Ph.D. NASA Johnson Space Center 
Feiveson, Alan  Ph.D. Collaborator: NASA Johnson Space Center 
Stenger, Michael  NASA Johnson Space Center 
Laurie, Steven  Ph.D. KBR/NASA Johnson Space Center 
Key Personnel Changes / Previous PI: August 2019 report: Steven Laurie, Ph.D. is CoInvestigator. January 2017: Remove Dr. Rob Ploutz-Snyder as CoInvestigator; Add: Dr. Alan Feiveson as Collaborator.
Project Information: Grant/Contract No. Internal Project 
Responsible Center: NASA JSC 
Grant Monitor: Stenger, Michael  
Center Contact: 281-483-1311 
michael.b.stenger@nasa.gov 
Solicitation / Funding Source: 2010 Crew Health NNJ10ZSA003N 
Grant/Contract No.: Internal Project 
Project Type: FLIGHT 
Flight Program: ISS 
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) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Cardiovascular:Risk of Cardiovascular Adaptations Contributing to Adverse Mission Performance and Health Outcomes (IRP Rev M)
Human Research Program Gaps: (1) CVD-101:To determine whether long-duration weightlessness induces cardiovascular structural and functional changes and/or oxidative stress & damage (OSaD)/inflammation, that can contribute to development of disease (IRP Rev L)
(2) CVD-103:To determine whether the combined effects of relevant deep-space radiation and weightlessness induce additive or synergistic effects on the cardiovascular system, and whether it is of concern for development of disease (IRP Rev L)
Flight Assignment/Project Notes: ISS

NOTE: End date changed to 8/31/2023 per HRP HHC element (Ed., 8/12/21)

Task Description: NOTE: Continuation of "Defining the Relation Between Biomarkers of Oxidative and Inflammatory Stress and Atherosclerosis Risk in Astronauts During and After Long-Duration Spaceflight" ; previous Principal Investigator was Dr. Steven Platts, until March 2016.

Atherosclerosis is the major contributor to cardiovascular disease-related morbidity and mortality. Research indicates that many of the risk factors commonly associated with atherosclerosis contribute to endothelial dysfunction, a process which presents early in life before angiographic evidence of disease and precedes the clinical manifestation of many cardiovascular disease-related disorders. In an effort to compensate for the initial risk factor-related disruptions to homeostasis, there is a compensatory upregulation of atheroprotective mechanisms. However, in the absence of appropriate risk factor management, these defense mechanisms may become overwhelmed and less able to reestablish normal function. Key systems that help maintain vascular homeostasis and are susceptible to differential deleterious alterations include those that help balance levels of oxidative and inflammatory stress. New evidence suggests that long-duration spaceflight may promote oxidative and inflammatory stress through mechanisms such as radiation exposure, diet, physical inactivity, and psychological stress. However, there are no data supporting a causal link between biomarkers of oxidative and inflammatory stress and indices of vascular endothelial dysfunction in spaceflight. As such, we proposed to examine the relation between biomarkers of oxidative and inflammatory stress and well-established measures of vascular endothelial dysfunction (flow mediated dilation (FMD)) and carotid intima-media thickness (cIMT) in astronauts before, during, and after long duration spaceflight.

Research Impact/Earth Benefits: It is well known that inflammation is a key contributor to the development of atherosclerosis. There is also emerging work showing the link with oxidative damage. This work may contribute to general clinical science by showing the interactions of multiple stressors in a unique environment (spaceflight).

Task Progress & Bibliography Information FY2021 
Task Progress: All pre-, in-, and immediate postflight data have been collected and analyzed. A manuscript describing these results has been published (Lee SMC et al. Arterial structure and function during and after long-duration spaceflight. J Appl Physiol 129: 108-123, 2020; see also Cumulative Bibliography), and a response was published (Lee SMC et al. Reply to Greaves et al. J Appl Physiol 129: 113, 2020) to a “Letter to the Editor” (Greaves DK, Robertson AD, Patterson CA, Au JS, Hughson RL. Evidence for increased cardiovascular risk to crew during long duration space missions. J Appl Physiol 129: 1111–1112, 2020) regarding this manuscript. Additionally, the investigators continue to participate in the annual Human Research Program Investigators’ Workshop.

Most astronauts continue to participate in postflight data collections, scheduled to extend to 5 years after landing, although a few are not readily available due to retirement from the astronaut corps or limited travel opportunities coming from international partner organizations, and two have discontinued participation. Thus, we expect that a total of 11 subjects will participate in data collection through 5 years after landing. To date, 3 astronauts have completed data collection through 5 years after landing, and 9 astronauts have completed their 3-year postflight test. Results from this study and previous reports have been used to inform the design of the NASA Standard Measures Study as well Human Research Program-defined risks associated with cardiovascular disease.

Bibliography Type: Description: (Last Updated: 03/21/2022) 

Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings Lee SMC, Ribeiro LC, Martin DS, Mercaldo ND, Smith SM, Zwart SR, Laurie SS, Macias BR, Stenger MB. "Indices of cardiovascular disease risk in astronauts after long-duration spaceflight in low Earth orbit." 2021 NASA Human Research Program Investigators’ Workshop, Virtual, February 1-4, 2021.

Abstracts. 2021 NASA Human Research Program Investigators’ Workshop, Virtual, February 1-4, 2021. , Feb-2021

Articles in Other Journals or Periodicals Lee SMC, Laurie SS, Macias BR, Zwart SR, Smith SM, Stenger MB. "Reply to Greaves et al. [Evidence for increased cardiovascular risk to crew during long duration space missions. Greaves DK, Robertson AD, Patterson CA, Au JS, Hughson RL. J Appl Physiol (1985). 2020 Nov 1;129(5):1111-2. PMID: 33197374] " J Appl Physiol (1985). 2020 Nov 1;129(5):1113. https://doi.org/10.1152/japplphysiol.00757.2020 ; PMID: 33197372; PMCID: PMC7790133 , Nov-2020
Project Title:  Defining the Relation Between Biomarkers of Oxidative and Inflammatory Stress and Atherosclerosis Risk in Astronauts During and After Long-Duration Spaceflight (PI=Lee) Reduce
Images: icon  Fiscal Year: FY 2020 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 03/01/2016  
End Date: 05/10/2022  
Task Last Updated: 09/29/2020 
Download report in PDF pdf
Principal Investigator/Affiliation:   Lee, Stuart M.C. Ph.D. / KBR/NASA Johnson Space Center 
Address:  2400 NASA Parkway 
 
Houston , TX 77058-2749 
Email: stuart.lee-1@nasa.gov 
Phone: 281-483-3726  
Congressional District: 36 
Web:  
Organization Type: NASA CENTER 
Organization Name: KBR/NASA Johnson Space Center 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Smith, Scott  Ph.D. NASA Johnson Space Center 
Feiveson, Alan  Ph.D. NASA Johnson Space Center 
Stenger, Michael  NASA Johnson Space Center 
Laurie, Steven  Ph.D. KBR/NASA Johnson Space Center 
Key Personnel Changes / Previous PI: August 2019 report: Steven Laurie, Ph.D. is CoInvestigator. January 2017: Remove Dr. Rob Ploutz-Snyder as CoInvestigator; Add: Dr. Alan Feiveson as Collaborator.
Project Information: Grant/Contract No. Internal Project 
Responsible Center: NASA JSC 
Grant Monitor: Norsk, Peter  
Center Contact:  
Peter.norsk@nasa.gov 
Solicitation / Funding Source: 2010 Crew Health NNJ10ZSA003N 
Grant/Contract No.: Internal Project 
Project Type: FLIGHT 
Flight Program: ISS 
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) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Cardiovascular:Risk of Cardiovascular Adaptations Contributing to Adverse Mission Performance and Health Outcomes (IRP Rev M)
Human Research Program Gaps: (1) CVD-101:To determine whether long-duration weightlessness induces cardiovascular structural and functional changes and/or oxidative stress & damage (OSaD)/inflammation, that can contribute to development of disease (IRP Rev L)
(2) CVD-103:To determine whether the combined effects of relevant deep-space radiation and weightlessness induce additive or synergistic effects on the cardiovascular system, and whether it is of concern for development of disease (IRP Rev L)
Flight Assignment/Project Notes: ISS

Task Description: NOTE: Continuation of "Defining the Relation Between Biomarkers of Oxidative and Inflammatory Stress and Atherosclerosis Risk in Astronauts During and After Long-Duration Spaceflight" ; previous Principal Investigator was Dr. Steven Platts, until March 2016.

Atherosclerosis is the major contributor to cardiovascular disease-related morbidity and mortality. Research indicates that many of the risk factors commonly associated with atherosclerosis contribute to endothelial dysfunction, a process which presents early in life before angiographic evidence of disease and precedes the clinical manifestation of many cardiovascular disease-related disorders. In an effort to compensate for the initial risk factor-related disruptions to homeostasis, there is a compensatory upregulation of atheroprotective mechanisms. However, in the absence of appropriate risk factor management, these defense mechanisms may become overwhelmed and less able to reestablish normal function. Key systems that help maintain vascular homeostasis and are susceptible to differential deleterious alterations include those that help balance levels of oxidative and inflammatory stress. New evidence suggests that long-duration spaceflight may promote oxidative and inflammatory stress through mechanisms such as radiation exposure, diet, physical inactivity, and psychological stress. However, there are no data supporting a causal link between biomarkers of oxidative and inflammatory stress and indices of vascular endothelial dysfunction in spaceflight. As such, we proposed to examine the relation between biomarkers of oxidative and inflammatory stress and well-established measures of vascular endothelial dysfunction (flow mediated dilation (FMD)) and carotid intima-media thickness (cIMT) in astronauts before, during, and after long duration spaceflight.

Research Impact/Earth Benefits: It is well known that inflammation is a key contributor to the development of atherosclerosis. There is also emerging work showing the link with oxidative damage. This work may contribute to general clinical science by showing the interactions of multiple stressors in a unique environment (spaceflight).

Task Progress & Bibliography Information FY2020 
Task Progress: INTRODUCTION: Long-duration missions onboard the International Space Station (ISS) and exploration class missions to the Moon, Mars, or a nearby asteroid expose astronauts to increased risk of oxidative and inflammatory damage. Oxidative stress and inflammation may result from a variety of sources, including radiation, psychological stress, reduced physical activity, altered nutritional status, and exposure to oxygen-rich environments, such as during extravehicular activity (space walks). Increased oxidative damage and inflammation accelerate the development of atherosclerosis, and thus could be a long-term health concern for astronauts. The purpose of this investigation is to determine (1) if biomarkers of oxidative and inflammatory stress measured in blood and urine are elevated with spaceflight, (2) if indices of increased atherosclerosis risk are present before, during, and after long duration spaceflight, and (3) if biomarkers of oxidative and inflammatory stress are related to indices of atherosclerosis risk in International Space Station (ISS) astronauts. This was the first study to propose assessing immediate and long-term risk for atherosclerosis using biochemical, structural, and functional measures before, during, immediately after, and up to five years after spaceflight.

METHODS: To meet the objectives of the study, 13 astronauts have been studied before, during, and up to 5 years after long duration missions aboard ISS. Levels of oxidative and inflammatory stress biomarkers, some of which we have previously shown to be elevated with spaceflight, were measured from blood and urine samples taken before, during, and after spaceflight. Arterial structure have been assessed before, during, and after spaceflight using measures of carotid artery wall thickness, while arterial function will be measured in the brachial artery before flight and after landing. Increased carotid artery wall thickness and decreased brachial artery function, measured using standard clinical ultrasound, are well-established indices of atherosclerosis risk.

RESULTS: While biomarkers of oxidative stress and inflammation are elevated during spaceflight, arterial structure and function were not changed by spaceflight. Biomarkers of oxidative stress and inflammation increased during spaceflight but most returned to preflight levels within 1 week after landing. Common carotid artery intima-media thickness, stiffness, and distensibility were not different than preflight at any time. As a group, neither mean endothelium-dependent nor -independent vasodilation changed from pre- to postflight. It is unclear whether future exploration missions, with an extended duration in altered gravity fields and increased radiation exposure may be problematic.

DISCUSSION: Here we report no significant change in common carotid and brachial arterial structure and function in 13 astronauts participating in long-duration spaceflights aboard the ISS. In general, biomarkers of inflammation and oxidative stress were elevated during the mission, but returned to preflight levels within a week of landing. Further, we examined the relation between the arterial adaptations to spaceflight in individual astronauts and some key biomarkers associated with cardiovascular disease risk and vascular remodeling. In this healthy population of middle-aged astronauts, we found only a weak association between changes in high sensitivity- CRP (Cardiac Rhythm Problems) and carotid artery changes within subjects. Spaceflight-induced changes in endothelium-independent vasodilation, in particular, were related to changes in some of the biomarkers of oxidative stress.

Bibliography Type: Description: (Last Updated: 03/21/2022) 

Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings Lee SMC, Ribeiro LC, Martin DS, Smith SM, Zwart SR, Laurie SS, Macias BR, Stenger MB. "Defining the Relationship between Biomarkers of Oxidative and Inflammatory Stress and the Risk for Atherosclerosis in Astronauts during and after Long-Duration Spaceflight." 2020 NASA Human Research Program Investigators’ Workshop, Galveston, TX, January 27-30, 2020.

Human Research Program Investigators’ Workshop, Human Exploration Small Steps Lead to Giant Leaps: Translating Research into Space Exploration. 2020 NASA Human Research Program Investigators’ Workshop, Galveston, TX, January 27-30, 2020. , Jan-2020

Articles in Peer-reviewed Journals Lee SMC, Ribeiro LC, Martin DS, Zwart SR, Feiveson AH, Laurie SS, Macias BR, Crucian BE, Krieger S, Weber D, Grune T, Platts SH, Smith SM, Stenger MB. "Arterial structure and function during and after long-duration spaceflight." J Appl Physiol (1985). 2020 Jul 1;129(1):108-23. https://doi.org/10.1152/japplphysiol.00550.2019 ; PMID: 32525433 , Jul-2020
Project Title:  Defining the Relation Between Biomarkers of Oxidative and Inflammatory Stress and Atherosclerosis Risk in Astronauts During and After Long-Duration Spaceflight (PI=Lee) Reduce
Images: icon  Fiscal Year: FY 2019 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 03/01/2016  
End Date: 05/10/2022  
Task Last Updated: 08/18/2019 
Download report in PDF pdf
Principal Investigator/Affiliation:   Lee, Stuart M.C. Ph.D. / KBR/NASA Johnson Space Center 
Address:  2400 NASA Parkway 
 
Houston , TX 77058-2749 
Email: stuart.lee-1@nasa.gov 
Phone: 281-483-3726  
Congressional District: 36 
Web:  
Organization Type: NASA CENTER 
Organization Name: KBR/NASA Johnson Space Center 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Smith, Scott  Ph.D. NASA Johnson Space Center 
Feiveson, Alan  Ph.D. NASA Johnson Space Center 
Stenger, Michael  NASA Johnson Space Center 
Laurie, Steven  Ph.D. KBR/NASA Johnson Space Center 
Key Personnel Changes / Previous PI: August 2019 report: Steven Laurie, Ph.D. is CoInvestigator. January 2017: Remove Dr. Rob Ploutz-Snyder as CoInvestigator; Add: Dr. Alan Feiveson as Collaborator.
Project Information: Grant/Contract No. Internal Project 
Responsible Center: NASA JSC 
Grant Monitor: Norsk, Peter  
Center Contact:  
Peter.norsk@nasa.gov 
Solicitation / Funding Source: 2010 Crew Health NNJ10ZSA003N 
Grant/Contract No.: Internal Project 
Project Type: FLIGHT 
Flight Program: ISS 
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) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Cardiovascular:Risk of Cardiovascular Adaptations Contributing to Adverse Mission Performance and Health Outcomes (IRP Rev M)
Human Research Program Gaps: (1) CVD-101:To determine whether long-duration weightlessness induces cardiovascular structural and functional changes and/or oxidative stress & damage (OSaD)/inflammation, that can contribute to development of disease (IRP Rev L)
(2) CVD-103:To determine whether the combined effects of relevant deep-space radiation and weightlessness induce additive or synergistic effects on the cardiovascular system, and whether it is of concern for development of disease (IRP Rev L)
Flight Assignment/Project Notes: ISS

Task Description: NOTE: Continuation of "Defining the Relation Between Biomarkers of Oxidative and Inflammatory Stress and Atherosclerosis Risk in Astronauts During and After Long-Duration Spaceflight" ; previous Principal Investigator was Dr. Steven Platts, until March 2016.

Atherosclerosis is the major contributor to cardiovascular disease-related morbidity and mortality. Research indicates that many of the risk factors commonly associated with atherosclerosis contribute to endothelial dysfunction, a process which presents early in life before angiographic evidence of disease and precedes the clinical manifestation of many cardiovascular disease-related disorders. In an effort to compensate for the initial risk factor-related disruptions to homeostasis, there is a compensatory upregulation of atheroprotective mechanisms. However, in the absence of appropriate risk factor management, these defense mechanisms may become overwhelmed and less able to reestablish normal function. Key systems that help maintain vascular homeostasis and are susceptible to differential deleterious alterations include those that help balance levels of oxidative and inflammatory stress. New evidence suggests that long-duration spaceflight may promote oxidative and inflammatory stress through mechanisms such as radiation exposure, diet, physical inactivity, and psychological stress. However, there are no data supporting a causal link between biomarkers of oxidative and inflammatory stress and indices of vascular endothelial dysfunction in spaceflight. As such, we propose to examine the relation between biomarkers of oxidative and inflammatory stress and well-established measures of vascular endothelial dysfunction (flow mediated dilation (FMD)) and carotid intima-media thickness (cIMT) in astronauts before, during, and after long duration spaceflight.

Research Impact/Earth Benefits: It is well known that inflammation is a key contributor to the development of atherosclerosis. There is also emerging work showing the link with oxidative damage. This work may contribute to general clinical science by showing the interactions of multiple stressors in a unique environment (spaceflight).

Task Progress & Bibliography Information FY2019 
Task Progress: All pre-, in-, and immediate postflight data have been collected and processed. A manuscript describing these results has been submitted for peer-review in a scientific journal. All astronauts are participating in postflight data collections, scheduled to extend to 5 years after landing. Half of the subjects have completed their 3-year postflight test. Results from this study and previous reports are being used to inform the NASA Standard Measures Study as well Human Research Program-defined risks associated with cardiovascular disease.

Bibliography Type: Description: (Last Updated: 03/21/2022) 

Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings Lee SMC, Ribeiro LC, Martin DS, Smith SM, Zwart SR, Laurie SS, Macias BR, Stenger MB. "Defining the Relationship between Biomarkers of Oxidative and Inflammatory Stress and the Risk for Atherosclerosis in Astronauts During and After Long-Duration Spaceflight." 2019 NASA Human Research Program Investigators’ Workshop, Galveston, TX, January 22-25, 2019.

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

Articles in Peer-reviewed Journals Garrett-Bakelman FE, Darshi M, Green SJ, Gur RC, Lin L, Macias BR, McKenna MJ, Meydan C, Mishra T, Nasrini J, Piening BD, Rizzardi LF, Sharma K, Siamwala JH, Taylor L, Vitaterna MH, Afkarian M, Afshinnekoo E, Ahadi S, Ambati A, Arya M, Bezdan D, Callahan CM, Chen S, Choi AMK, Chlipala GE, Contrepois K, Covington M, Crucian BE, De Vivo I, Dinges DF, Ebert DJ, Feinberg JI, Gandara JA, George KA, Goutsias J, Grills GS, Hargens AR, Heer M, Hillary RP, Hoofnagle AN, Hook VYH, Jenkinson G, Jiang P, Keshavarzian A, Laurie SS, Lee-McMullen B, Lumpkins SB, MacKay M, Maienschein-Cline MG, Melnick AM, Moore TM, Nakahira K, Patel HH, Pietrzyk R, Rao V, Saito R, Salins DN, Schilling JM, Sears DD, Sheridan CK, Stenger MB, Tryggvadottir R, Urban AE, Vaisar T, Van Espen B, Zhang J, Ziegler MG, Zwart SR, Charles JB, Kundrot CE, Scott GBI, Bailey SM, Basner M, Feinberg AP, Lee SMC, Mason CE, Mignot E, Rana BK, Smith SM, Snyder MP, Turek FW. "The NASA Twins Study: A multidimensional analysis of a year-long human spaceflight." Science. 2019 Apr 12;364(6436):eaau8650. https://science.sciencemag.org/content/364/6436/eaau8650.long ; PubMed PMID: 30975860 , Apr-2019
Project Title:  Defining the Relation Between Biomarkers of Oxidative and Inflammatory Stress and Atherosclerosis Risk in Astronauts During and After Long-Duration Spaceflight (PI=Lee) Reduce
Images: icon  Fiscal Year: FY 2017 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 03/01/2016  
End Date: 05/10/2022  
Task Last Updated: 01/22/2017 
Download report in PDF pdf
Principal Investigator/Affiliation:   Lee, Stuart M.C. Ph.D. / KBR/NASA Johnson Space Center 
Address:  2400 NASA Parkway 
 
Houston , TX 77058-2749 
Email: stuart.lee-1@nasa.gov 
Phone: 281-483-3726  
Congressional District: 36 
Web:  
Organization Type: NASA CENTER 
Organization Name: KBR/NASA Johnson Space Center 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Smith, Scott  Ph.D. NASA Johnson Space Center 
Feiveson, Alan  Ph.D. NASA Johnson Space Center 
Stenger, Michael  Ph.D. NASA Johnson Space Center 
Key Personnel Changes / Previous PI: January 2017: Remove Dr. Rob Ploutz-Snyder as CoInvestigator; Add: Dr. Alan Feiveson.
Project Information: Grant/Contract No. Internal Project 
Responsible Center: NASA JSC 
Grant Monitor: Allcorn, Aaron  
Center Contact: 281.244.8402 
aaron.j.allcorn@nasa.gov 
Solicitation / Funding Source: 2010 Crew Health NNJ10ZSA003N 
Grant/Contract No.: Internal Project 
Project Type: FLIGHT 
Flight Program: ISS 
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) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Cardiovascular:Risk of Cardiovascular Adaptations Contributing to Adverse Mission Performance and Health Outcomes (IRP Rev M)
Human Research Program Gaps: (1) CVD-101:To determine whether long-duration weightlessness induces cardiovascular structural and functional changes and/or oxidative stress & damage (OSaD)/inflammation, that can contribute to development of disease (IRP Rev L)
(2) CVD-103:To determine whether the combined effects of relevant deep-space radiation and weightlessness induce additive or synergistic effects on the cardiovascular system, and whether it is of concern for development of disease (IRP Rev L)
Flight Assignment/Project Notes: ISS

Task Description: NOTE: Continuation of "Defining the Relation Between Biomarkers of Oxidative and Inflammatory Stress and Atherosclerosis Risk in Astronauts During and After Long-Duration Spaceflight" ; previous Principal Investigator was Dr. Steven Platts until March 2016.

Atherosclerosis is the major contributor to cardiovascular disease-related morbidity and mortality. Research indicates that many of the risk factors commonly associated with atherosclerosis contribute to endothelial dysfunction, a process which presents early in life before angiographic evidence of disease and precedes the clinical manifestation of many cardiovascular disease-related disorders. In an effort to compensate for the initial risk factor-related disruptions to homeostasis, there is a compensatory upregulation of atheroprotective mechanisms. However, in the absence of appropriate risk factor management, these defense mechanisms may become overwhelmed and less able to reestablish normal function. Key systems that help maintain vascular homeostasis and are susceptible to differential deleterious alterations include those that help balance levels of oxidative and inflammatory stress. New evidence suggests that long-duration spaceflight may promote oxidative and inflammatory stress through mechanisms such as radiation exposure, diet, physical inactivity, and psychological stress. However, there are no data supporting a causal link between biomarkers of oxidative and inflammatory stress and indices of vascular endothelial dysfunction in spaceflight. As such, we propose to examine the relation between biomarkers of oxidative and inflammatory stress and well-established measures of vascular endothelial dysfunction (flow mediated dilation (FMD)) and carotid intima-media thickness (cIMT) in astronauts before, during, and after long duration spaceflight.

Research Impact/Earth Benefits: It is well known that inflammation is a key contributor to the development of atherosclerosis. There is also emerging work showing the link with oxidative damage. This work may contribute to general clinical science by showing the interactions of multiple stressors in a unique environment (spaceflight).

Task Progress & Bibliography Information FY2017 
Task Progress: Pre-, in-, and immediately post-flight data collection has been completed for all but one astronaut participating in this experiment. The final in- and immediate post-flight data collection will be completed in the spring of 2017. Five astronauts have completed R+1 yr testing but none have participated in R+3 yr tests.

Data analysis is in progress. Data shared through required medical testing is being secured.

Bibliography Type: Description: (Last Updated: 03/21/2022) 

Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings Lee SMC, Martin DS, Smith SM, Zwart SR, Laurie SS, Ribeiro LC, Stenger MB. "Defining the relationship between biomarkers of oxidative and inflammatory stress and the risk for atherosclerosis in astronauts during and after long duration spaceflight." 2017 NASA Human Research Program Investigators’ Workshop, Galveston, TX, January 23-26, 2017.

2017 NASA Human Research Program Investigators’ Workshop, Galveston, TX, January 23-26, 2017. , Jan-2017

Abstracts for Journals and Proceedings Lee SMC, Martin DS, Laurie SS, Ribeiro LC, Smith SM, Zwart SR, Stenger MB. "Carotid artery structure during and after long-duration space flight." To be presented at Experimental Biology 2017: Transforming the Future through Science, Chicago, IL, April 22-26, 2017.

Experimental Biology 2017, Chicago, IL, April 22-26, 2017. , Apr-2017

Project Title:  Defining the Relation Between Biomarkers of Oxidative and Inflammatory Stress and Atherosclerosis Risk in Astronauts During and After Long-Duration Spaceflight (PI=Lee) Reduce
Images: icon  Fiscal Year: FY 2016 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 03/01/2016  
End Date: 05/10/2022  
Task Last Updated: 05/10/2016 
Download report in PDF pdf
Principal Investigator/Affiliation:   Lee, Stuart M.C. Ph.D. / KBR/NASA Johnson Space Center 
Address:  2400 NASA Parkway 
 
Houston , TX 77058-2749 
Email: stuart.lee-1@nasa.gov 
Phone: 281-483-3726  
Congressional District: 36 
Web:  
Organization Type: NASA CENTER 
Organization Name: KBR/NASA Johnson Space Center 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Ploutz-Snyder, Robert  Ph.D. Universities Space Research Association 
Smith, Scott  Ph.D. NASA Johnson Space Center 
Stenger, Michael  Ph.D. Wyle Science, Technology, and Engineering Group 
Project Information: Grant/Contract No. Internal Project 
Responsible Center: NASA JSC 
Grant Monitor: Allcorn, Aaron  
Center Contact: 281.244.8402 
aaron.j.allcorn@nasa.gov 
Solicitation / Funding Source: 2010 Crew Health NNJ10ZSA003N 
Grant/Contract No.: Internal Project 
Project Type: FLIGHT 
Flight Program: ISS 
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) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Cardiovascular:Risk of Cardiovascular Adaptations Contributing to Adverse Mission Performance and Health Outcomes (IRP Rev M)
Human Research Program Gaps: (1) CVD-101:To determine whether long-duration weightlessness induces cardiovascular structural and functional changes and/or oxidative stress & damage (OSaD)/inflammation, that can contribute to development of disease (IRP Rev L)
(2) CVD-103:To determine whether the combined effects of relevant deep-space radiation and weightlessness induce additive or synergistic effects on the cardiovascular system, and whether it is of concern for development of disease (IRP Rev L)
Task Description: NOTE: Continuation of "Defining the Relation Between Biomarkers of Oxidative and Inflammatory Stress and Atherosclerosis Risk in Astronauts During and After Long-Duration Spaceflight" ; previous Principal Investigator was Dr. Steven Platts until March 2016.

Atherosclerosis is the major contributor to cardiovascular disease-related morbidity and mortality. Research indicates that many of the risk factors commonly associated with atherosclerosis contribute to endothelial dysfunction, a process which presents early in life before angiographic evidence of disease and precedes the clinical manifestation of many cardiovascular disease-related disorders. In an effort to compensate for the initial risk factor-related disruptions to homeostasis, there is a compensatory upregulation of atheroprotective mechanisms. However, in the absence of appropriate risk factor management, these defense mechanisms may become overwhelmed and less able to reestablish normal function. Key systems that help maintain vascular homeostasis and are susceptible to differential deleterious alterations include those that help balance levels of oxidative and inflammatory stress. New evidence suggests that long-duration spaceflight may promote oxidative and inflammatory stress through mechanisms such as radiation exposure, diet, physical inactivity, and psychological stress. However, there are no data supporting a causal link between biomarkers of oxidative and inflammatory stress and indices of vascular endothelial dysfunction in spaceflight. As such, we propose to examine the relation between biomarkers of oxidative and inflammatory stress and well-established measures of vascular endothelial dysfunction (flow mediated dilation (FMD)) and carotid intima-media thickness (cIMT) in astronauts before, during, and after long duration spaceflight.

Research Impact/Earth Benefits: It is well known that inflammation is a key contributor to the development of atherosclerosis. There is also emerging work showing the link with oxidative damage. This work may contribute to general clinical science by showing the interactions of multiple stressors in a unique environment (spaceflight).

Task Progress & Bibliography Information FY2016 
Task Progress: New project for FY2016.

Continuation of "Defining the Relation Between Biomarkers of Oxidative and Inflammatory Stress and Atherosclerosis Risk in Astronauts During and After Long-Duration Spaceflight" ; previous Principal Investigator was Dr. Steven Platts until March 2016. See that project for previous reporting.

Bibliography Type: Description: (Last Updated: 03/21/2022) 

Show Cumulative Bibliography Listing
 
 None in FY 2016