# Endothelial Cell Health Across the Spectrum of Cardiometabolic Disease

> **NIH NIH R01** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2024 · $123,849

## Abstract

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.

## Key facts

- **NIH application ID:** 11094301
- **Project number:** 3R01HL168889-02S1
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** Naomi Miriam Hamburg
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $123,849
- **Award type:** 3
- **Project period:** 2023-09-12 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11094301

## Citation

> US National Institutes of Health, RePORTER application 11094301, Endothelial Cell Health Across the Spectrum of Cardiometabolic Disease (3R01HL168889-02S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/11094301. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*