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Mitochondria-targeted antioxidant supplementation for improving age-related vascular dysfunction in older adults: the role of circulating factors

Award Number: F32HL167552
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 09/30/2023
PERIOD OF PERFORMANCE END DATE: 03/29/2025

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Mitochondria-targeted antioxidant supplementation for improving age-related vascular dysfunction in older adults: the role of circulating factors - PROJECT SUMMARY/ABSTRACT The purpose of this F32 application is to support Dr. Kevin Murray, a promising first-year postdoctoral fellow in the laboratory of Dr. Douglas Seals, to conduct original research and receive scientific training that will prepare him to become an independent, extramurally funded investigator in the field of translational vascular physiology aimed at identifying novel interventions for improving vascular function with aging and the associated mechanisms of action. Dr. Murray will learn a variety of new technical, conceptual, and professional skills, including focused training in translational cellular and molecular vascular physiology research, in addition to training in conducting a clinical trial. His proposed research project will leverage his primary sponsor’s ongoing NIH-funded R01-funded clinical trial that seeks to establish the efficacy of the mitochondria-targeted antioxidant MitoQ for improving vascular endothelial function in older adults to determine (Aim 1) whether changes in the circulating milieu following 3 months of chronic treatment with MitoQ improves endothelial cell function by treating human aortic endothelial cells (HAECs) with plasma collected from subjects after MitoQ or placebo treatment. He will also determine (Aim 2) if reductions in oxidized low-density lipoprotein (oxLDL) following MitoQ treatment mediate improvements in endothelial cell function by ameliorating oxLDL-stimulated mitochondrial fission. Lastly, he will also explore (Aim 3) the role of changes in extracellular vesicles (EVs) with MitoQ treatment in mediating improvements in endothelial cell function and whether these potential changes are associated with alterations to miRNA content of EVs. Age-related endothelial dysfunction is largely mediated by reduced bioavailability of the vasoprotective molecule, nitric oxide (NO), as a result of excessive production of reactive oxygen species (ROS). Dysfunctional mitochondria increase with age and are a major source of excess ROS (mtROS) in the vasculature. MitoQ is a mitochondrial-targeted antioxidant and our laboratory previously showed that 6-weeks of MitoQ supplementation in older adults improved NO-mediated endothelium-dependent dilation. Preliminary data collected by Dr. Murray for this application suggest that changes to the circulating milieu following MitoQ treatment increase NO bioavailability and decrease mtROS bioactivity in HAECs ex vivo, extending the mechanisms of action by which MitoQ supplementation improves endothelial function. Guided by these strong preliminary data, Dr. Murray will aim to establish changes to the circulating milieu as a mechanism of action by which MitoQ treatment improves endothelial function by leveraging plasma samples collected from subjects during his primary sponsor’s ongoing NIH-funded R01 clinical trial. The primary sponsor is an internationally recognized, NIH-funded scientist with a strong history of successful mentoring in translational biomedical research. With his guidance, and that of his mentoring team, Dr. Murray will be able to successfully complete the proposed research and training plan, preparing him to succeed as an extramurally funded independent investigator in translational vascular physiology.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = -$4,521 )
2026	2024	THE REGENTS OF THE UNIVERSITY OF COLORADO	3100 MARINE ST	BOULDER	CO	80303	BOULDER	USA	Cardiovascular Diseases Research	000	2	1/27/2026	NON-COMPETING CONTINUATION	-$4,521
														Subtotal = -$4,521

Issue Date FY: 2024 ( Subtotal = $41,378 )
2024	2024	THE REGENTS OF THE UNIVERSITY OF COLORADO	3100 MARINE ST	BOULDER	CO	80309	BOULDER	USA	Cardiovascular Diseases Research	000	2	8/15/2024	NON-COMPETING CONTINUATION	$41,378
														Subtotal = $41,378

Issue Date FY: 2023 ( Subtotal = $72,000 )
2023	2023	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST STE 481 572 UCB	BOULDER	CO	80309	BOULDER	USA	Cardiovascular Diseases Research	001	1	8/22/2023	NEW	$0
2023	2023	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST STE 481 572 UCB	BOULDER	CO	80309	BOULDER	USA	Cardiovascular Diseases Research	000	1	8/22/2023	NEW	$72,000
														Subtotal = $72,000

Grand Total All Awards = $108,857

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Mitochondria-targeted antioxidant supplementation for improving age-related vascular dysfunction in older adults: the role of circulating factors

Award Number: F32HL167552

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 09/30/2023

PERIOD OF PERFORMANCE END DATE: 03/29/2025

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