# Angiogenesis Protection Induced by sFRP3 Myocyte/Vascular Cross-Talk

> **NIH NIH R01** · RBHS-NEW JERSEY MEDICAL SCHOOL · 2020 · $564,480

## Abstract

Project Summary
Over the past half century there have been hundreds, if not thousands, of studies identifying cardioprotective
agents, but relatively few have progressed to the clinics. There are probably several reasons for this lack of
translational success: 1. That models identifying these potential cardioprotective mechanisms are based on
acute experiments, not similar to chronic ischemia in patients; 2. many prior protective mechanisms cannot
induce angiogenesis/arteriogenesis, which is required for patients with chronic myocardial ischemia and limited
coronary blood flow; and 3. the data were derived solely from rodent models. The current application is based
on the discovery of a novel cardioprotective agent, sFRP3, which was found in pigs with chronic
preconditioning. Although relatively little is known about this gene in heart disease, it has been also found to be
upregulated in patients with heart disease, which stimulated prior studies to conclude that sFRP3 exerted an
adverse effect in heart failure, a conclusion diametrically opposed to our hypothesis and preliminary data. One
of the major limitations to clinical translation of prior cardioprotective agents, is the inability to improve
myocardial blood flow to the chronically ischemic heart by inducing angiogenesis/arteriogenesis. Our
preliminary data indicate that sFRP3 induces both angiogenesis and arteriogenesis, which makes it an
important new mechanism designed for not only acute cardioprotection, but also protects against chronic
myocardial ischemic disease and finally will be of use to protect other organs where compromised blood flow
induces disease, e.g., peripheral arterial and cerebral vascular disease. We will study 2 major hypotheses:
Hypothesis A: sFRP3, when overexpressed either by injection into the heart, or genetically, exerts an
important protective effect on coronary vessels, by induction of angiogenesis/arteriogenesis.
Hypothesis B: sFRP3 induced protection against acute coronary artery occlusion is mediated by novel
signaling mechanisms rather than angiogenesis/arteriogenesis.

## Key facts

- **NIH application ID:** 9900045
- **Project number:** 5R01HL137405-04
- **Recipient organization:** RBHS-NEW JERSEY MEDICAL SCHOOL
- **Principal Investigator:** STEPHEN F VATNER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $564,480
- **Award type:** 5
- **Project period:** 2017-04-15 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9900045

## Citation

> US National Institutes of Health, RePORTER application 9900045, Angiogenesis Protection Induced by sFRP3 Myocyte/Vascular Cross-Talk (5R01HL137405-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9900045. Licensed CC0.

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