# Platelets in vascular injury repair

> **NIH NIH R01** · YALE UNIVERSITY · 2020 · $563,947

## Abstract

PROJECT SUMMARY/ABSTRACT
Percutaneous arterial interventions and arterial bypass surgeries are complicated by the problem of intimal
hyperplasia (restenosis). Diabetic patients are more likely to experience restenosis, even after drug-eluting
stents. With ever increasing numbers of intravascular (e.g. angioplasty and insertion of devices) and
surgical procedures (e.g. bypass) for highly prevalent cardiovascular diseases, optimal resolution of repair
is essential. The process of arterial repair after injury is complex. Initiation of repair after injury is well
studied with thrombosis followed by inflammation, cellular proliferation and remodeling. Resolution of the
repair process is poorly understood, particularly, what constitutes the “brake” to prevent excessive repair?
Platelets provide a first and crucial line of defense against vascular injury, initially maintaining hemostasis.
Upon activation, platelets also release bioactive mediators such as PDGF and thromboxane, promoting
VSMC dedifferentiation from a quiescent contractile phenotype to a highly synthetic and proliferating cell
type, promoting injury repair. Excessive repair, such as observed with intimal hyperplasia in diabetes
mellitus (DM) after surgical or vascular interventions, can result from enhanced VSMC dedifferentiation and
proliferation. We will address the hypothesis that horizontal transfer of platelet-derived miRNAs into VSMCs
provide a novel mechanism for regulating VSMC phenotypic switching, preventing excessive repair and
intimal hyperplasia. We are in a unique position to address our hypothesis with recognized surgical
expertise in vascular surgical interventions and VSMC biology (Alan Dardik MD and Kathleen Martin PhD),
platelet expertise (John Hwa MD PhD, Wai Ho Tang PhD), and diabetes mellitus (Silvio Inzucchi MD,
Raimund Herzog MD). In the short term we will have presented a novel mechanism for platelet-VSMC
interaction and arterial injury repair. In the long term, these mechanistic insights may provide new
therapeutic targets in promoting arterial injury repair.

## Key facts

- **NIH application ID:** 9874977
- **Project number:** 1R01HL150515-01
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** JOHN HWA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $563,947
- **Award type:** 1
- **Project period:** 2020-02-15 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9874977

## Citation

> US National Institutes of Health, RePORTER application 9874977, Platelets in vascular injury repair (1R01HL150515-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9874977. Licensed CC0.

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