# FOG2 isoforms in Coronary Microvascular Disease

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2024 · $635,745

## Abstract

PROJECT SUMMARY
Coronary Microvascular Disease (CMVD), defined as disease of the coronary pre-arterioles, arterioles, and
capillaries, accounts for 30-50% of the burden of Ischemic Heart Disease (IHD). However, little is known about
the pathogenesis and there are no targeted therapies. Friend of Gata 2 (FOG2) is a cardiomyocyte
transcriptional co-regulator which is crucial for both the development and maintenance of the coronary
microvasculature. FOG2 promotes expression of angiogenic genes and inhibits expression of anti-angiogenic
genes, however, there are two predominant isoforms of FOG2, and the mechanism by which FOG2 promotes
an angiogenic program is not known. Our central hypothesis that cardiomyocyte FOG2S is the isoform which
regulates a pro-angiogenic gene program to support coronary microvasculature, via interactions with HIF1a.
Our objectives in this proposal are to define the structure-function relationship of FOG2 isoforms and HIF1a
and establish the paracrine effects of cardiomyocyte FOG2 and FOG2S on heterotypic vascular cells
phenotypes, as outlined in the following two aims. In Aim 1, we will determine the structure-function
relationship between FOG2 and HIF1a using co-immunoprecipitations studies and luciferase constructs for
angiogenic gene promoters. We will also establish the genome-wide cistrome of FOG2 isoforms. In Aim 2, we
will determine the paracrine effects of cardiomyocyte FOG2S on vascular cells in vivo and in vitro. First we use
a new isoform-specific inducible knockdown model we have developed to define the role of FOG2S in
maintaining the coronary microcirculation in vivo. We then establish the ability of cardiomyocyte FOG2S, as
opposed to FOG2, to regulate endothelial and smooth muscle cell proliferation, migration, and angiogenic
potential. Our studies will provide novel insight into mechanisms of coronary microvascular homeostasis. The
proposal's outcomes will fill a critical gap in understanding the molecular factors maintaining the coronary
microvasculature and shed light on mechanisms relevant to a significant portion of IHD.

## Key facts

- **NIH application ID:** 10944715
- **Project number:** 1R01HL175485-01
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Marie A Guerraty
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $635,745
- **Award type:** 1
- **Project period:** 2024-07-01 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10944715

## Citation

> US National Institutes of Health, RePORTER application 10944715, FOG2 isoforms in Coronary Microvascular Disease (1R01HL175485-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10944715. Licensed CC0.

---

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