# PKD3 and Valvular Heart Disease

> **NIH NIH R56** · UNIVERSITY OF ROCHESTER · 2024 · $581,493

## Abstract

Valvular Heart Disease (VHD) encompasses a number of common cardiovascular conditions that account for
10% to 20% of all cardiac surgical procedures in the United States. A better understanding of the heart valvular
disorders and underlying molecular mechanisms is important to aid in the management and treatment of
patients with VHD. Endothelial mesenchymal transition (EndMT) is a complex biological process in which
endothelial cells progressively evolve into cells with a mesenchymal phenotype. EndMT plays an essential role
in cardiac valve formation and function, and EndMT is temporally and spatially regulated during organ
development and maintenance. Abnormal EndMT is critically implicated in the pathogenesis of both congenital
cardiac valve disease and late-onset cardiac valve dysfunction. Thus, further understanding exact molecular
pathways that control EndMT during cardiac valve development and maintenance is likely to be significant in
order to develop therapeutic strategies to ameliorate heart valve disease. It has been well-established that
vascular endothelial growth factor (VEGF), one of the most potent regulators of angiogenesis, also plays a key
role in control of EndMT during cardiac valve development. A series of our previous studies have demonstrated
that a newly discovered serine/threonine protein kinas family members of protein kinase D (PKD), are key
signal molecules in mediating VEGF signaling and function. The nascent data from our recent preliminary
studies suggested a key role of protein kinase D3 (PKD3, gene name Prkd3) in regulation of EndMT and VHD.
In current application, we will determine how PKD3 regulates EndMT and heart valve development,
physiological function and pathological changes, and how to manipulate the PKD3-dependent signaling
pathways to prevent excessive EndMT and cardiac valve enlargement, ultimately, leading to new approaches
to treat VHD. Upon completion of the proposed studies, it will have significant impact on our understanding of
EndMT and cardiac valve development and function, and provide valuable information on the underlying
molecular mechanisms of cardiac valve development and abnormal factors for VHD, which will help to design
new therapeutic strategies for combating VHD. Recently, as part of the National Heart, Lung, and Blood
Institute (NHLBI)’s implementation of the Cardiovascular Advances in Research and Opportunities Legacy
(CAROL) Act, NHLBI issued a Notice of Special Interest to seek R01 applications that propose research in
valvular heart disease (NOT-HL-23-079). Thus, our work is extremely important and highly relevant to NHLBI’s
mission to elucidate the pathophysiology of VHD and to reduce the burdens of human heart disease.

## Key facts

- **NIH application ID:** 11135716
- **Project number:** 1R56HL174537-01
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** ZHENG-GEN JIN
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $581,493
- **Award type:** 1
- **Project period:** 2024-08-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11135716

## Citation

> US National Institutes of Health, RePORTER application 11135716, PKD3 and Valvular Heart Disease (1R56HL174537-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/11135716. Licensed CC0.

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