# Single-cell, multi-omic investigation of epicardial adipose and coronary endothelial dysfunction in type 1 diabetes

> **NIH NIH U01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2024 · $1,008,750

## Abstract

Abstract
Cardiovascular disease (CVD) is the leading cause of mortality in patients with Type 1 Diabetes (T1D), driven
by complex pathophysiological dysfunctions that remain poorly understood at the cellular and molecular level.
Epicardial fat accumulation and dysfunction have recently emerged as significant contributors to coronary artery
disease (CAD) in T1D, potentially by inducing coronary artery endothelial dysfunction through pro-inflammatory
adipocytokine secretion. This project utilizes the CARE-T1D consortium tissue bank to investigate the cellular
and molecular dysfunctions in epicardial fat and coronary vasculature in T1D. Specifically, we hypothesize that
T1D induces dysfunction in epicardial adipocytes, causing the release of inflammatory adipocytokines that traffic
to coronary endothelial cells disrupting their function. We propose to:
1) Comprehensively identify T1D-specific cell states and regulators in epicardial fat and coronary arteries by
performing single cell epigenetic and RNA profiling on CARE-T1D flash-frozen samples.
2) Genetically program “induced” T1D adipocytes in vitro to functionally characterize diabetes-specific adipocyte
cellular responses and identify dysregulated adipocytokines.
3) Integrate CARE-T1D coronary vascular profiles with functional genomic perturbations in endothelial cells to
define molecular mechanisms of T1D-specific endothelial dysfunction and test identified adipocytokines on
endothelial functions such as angiogenesis, adhesion and migration.
This research promises to elucidate the cellular mechanisms of CVD in T1D, offering insights into novel
therapeutic targets and a genomic atlas of single cell resolution data for future investigation.

## Key facts

- **NIH application ID:** 11074419
- **Project number:** 1U01DK142338-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** RAJAT M GUPTA
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,008,750
- **Award type:** 1
- **Project period:** 2024-09-18 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11074419

## Citation

> US National Institutes of Health, RePORTER application 11074419, Single-cell, multi-omic investigation of epicardial adipose and coronary endothelial dysfunction in type 1 diabetes (1U01DK142338-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11074419. Licensed CC0.

---

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