Monday, November 3, 2025 11/3/2025

Endothelial Cell Health Across the Spectrum of Cardiometabolic Disease

Award Number: R01HL168889
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/12/2023
PERIOD OF PERFORMANCE END DATE: 05/31/2028

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Endothelial Cell Health Across the Spectrum of Cardiometabolic Disease - Project Summary/Abstract The escalating prevalence of cardiometabolic risk factors including obesity and type 2 diabetes mellitus (T2DM) presents a critical cardiovascular challenge. Individuals with cardiometabolic disease harbor greater risk of cardiovascular disease (CVD) including accelerated vascular aging and premature atherosclerotic disease. Importantly, alterations in endothelial function predate the development of clinical CVD, making the vascular endothelium an important potential target for cardioprotection. Experimental studies and our prior work link altered metabolism to organelle stress including mitochondrial dysfunction and ER stress. In this proposal, we hypothesize that organelle stress induced by cardiometabolic traits drives vascular dysfunction and promotes CVD. We will leverage the unique resources of the planned Framingham Heart Study fourth examination cycle to prospectively collect fresh human endothelial cells (EC) from 2000 individuals. In Aim 1, we will investigate the association of T2DM and cardiometabolic traits with EC phenotype including organelle stress and nitric oxide signaling in a nested case-control sample of 450 individuals. In Aim 2, we will measure EC gene expression levels using RNA sequencing in 900 participants to identify and prioritize EC transcriptional programs linked to EC health phenotypes, cardiometabolic traits, and systemic metabolism. This proposal leverages a unique and highly experienced multidisciplinary team of investigators with expertise in obesity-related cardiovascular disease, endothelial biology, population science, translational patient-oriented research, multi-omics and bioinformatics. The proposed work will dwarf past efforts at defining endothelial health across disease states and will combine new deep phenotyping of EC conducted at scale in a community-based cohort with existing rigorous measures of cardiovascular health including metabolite profiles and genomic markers. These studies have the potential to provide important insights into mechanisms driving endothelial dysfunction and develop an unprecedented resource that will benefit vascular biology research.


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: 2025 ( Subtotal = $759,238 )
2025	2025	TRUSTEES OF BOSTON UNIVERSITY	85 EAST NEWTON ST # M-921	BOSTON	MA	02118	SUFFOLK	USA	Cardiovascular Diseases Research	001	3	7/30/2025	NON-COMPETING CONTINUATION	$759,238
2025	2024	TRUSTEES OF BOSTON UNIVERSITY	85 EAST NEWTON ST # M-921	BOSTON	MA	02118	SUFFOLK	USA	Cardiovascular Diseases Research	000	2	6/17/2025	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $759,238

Issue Date FY: 2024 ( Subtotal = $853,596 )
2024	2024	TRUSTEES OF BOSTON UNIVERSITY	85 EAST NEWTON ST # M-921	BOSTON	MA	02118	SUFFOLK	USA	Cardiovascular Diseases Research	001	2	6/11/2024	NON-COMPETING CONTINUATION	$729,747
2024	2024	TRUSTEES OF BOSTON UNIVERSITY	85 EAST NEWTON ST # M-921	BOSTON	MA	02118	SUFFOLK	USA	Cardiovascular Diseases Research	002	2	9/11/2024	SUPPLEMENT FOR EXPANSION	$123,849
2024	2023	TRUSTEES OF BOSTON UNIVERSITY	85 EAST NEWTON ST # M-921	BOSTON	MA	02118	SUFFOLK	USA	Cardiovascular Diseases Research	000	1	11/2/2023	NEW	$0
														Subtotal = $853,596

Issue Date FY: 2023 ( Subtotal = $752,931 )
2023	2023	TRUSTEES OF BOSTON UNIVERSITY	85 EAST NEWTON ST # M-921	BOSTON	MA	02118	SUFFOLK	USA	Cardiovascular Diseases Research	000	1	9/12/2023	NEW	$752,931
														Subtotal = $752,931

Grand Total All Awards = $2,365,765

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Endothelial Cell Health Across the Spectrum of Cardiometabolic Disease

Award Number: R01HL168889

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/12/2023

PERIOD OF PERFORMANCE END DATE: 05/31/2028

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