# miR 92/19 cluster in the ERK context

> **NIH NIH P01** · YALE UNIVERSITY · 2020 · $488,271

## Abstract

Project Summary:
 Recent work has shown that arterial levels of shear stress induce components of the miR-17-92 cluster
and antagonizing miR-92a enhances arteriogenesis, improves endothelial function and prevents vascular
inflammation in vivo. We have shown in exciting preliminary data that the genetic the loss of the miR 17-92
cluster in EC increases arteriogenesis in the hearts and limbs of mice. Remarkably, in aged mice with defective
collateralization, neutralization of miR-19a/b improves functional recovery of blood flow after hindlimb ischemia
(HLI) and de-represses the expression of genes that promote arteriogenesis. In addition, since both shear and
VEGF can activate ERK, data has shown that VEGF-A induces the miR-17-92 cluster via ERK1/2 signaling
and components of the cluster physiologically repress gene expression that regulates angiogenesis. Thus,
these data imply that hemodynamics and VEGF signaling converge on the miR 17-92 cluster to fine tune
arteriogenic and angiogenic gene expression in EC. Thus, we hypothesize that miR-92a and miR-19a work in
concert to govern arterial remodeling by repressing the expression of genes that synergize to promote
structural and functional arteriogenesis. To test this hypothesis, the following specific aims are proposed: 1:
Elucidate the role of miR-92a and miR-19a/b during arteriogenesis using genetic and pharmacological
strategies; 2: Examine the importance of ERK crosstalk with the WNT signaling pathway in regulating
arteriogenesis and 3: Identify the unique and common targets of miR 92a and miR-19a/b in EC both in vitro
and in vivo, using next generation sequencing technology.

## Key facts

- **NIH application ID:** 9939660
- **Project number:** 5P01HL107205-08
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** William C Sessa
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $488,271
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9939660

## Citation

> US National Institutes of Health, RePORTER application 9939660, miR 92/19 cluster in the ERK context (5P01HL107205-08). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9939660. Licensed CC0.

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