# 12-HETrE regulation of blood coagulation, hemostasis, and thrombosis

> **NIH NIH R35** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 · $20,577

## Abstract

ABSTRACT
Cardiovascular disease remains the main cause of death in the world, where 17.9 million people die every
year. Platelet activation plays a primary role in the pathophysiology of cardiovascular disease, especially in
atherosclerosis, and the inability to regulate platelet function leads to atherothrombotic events resulting in
myocardial infarction and stroke. Currently available antiplatelet agents inhibit platelet aggregation at the great
risk of bleeding. In our lab, we have identified the 12-LOX derived DGLA product, 12-HETrE, to potently inhibit
platelet activation ex vivo and significantly prevented occlusive thrombus formation in vivo. Interestingly, due to
its potent antithrombotic activities of 12-HETrE, investigations on its impact on normal hemostasis uncovered
that there were no differences in bleeding occurrences between treated and control groups. Further studies
revealed that 12-HETrE mediated its antiplatelet effects in part through the prostacyclin receptor and possibly
through other G⍺s-linked G-protein-coupled receptors. These studies highlight the potential for further studies
into the mechanisms of 12-HETrE which could lead to further discoveries of potential targets for the
development of antiplatelet therapies that will not lead to unnecessary bleeding risks. Previously, we have
identified bioactive synthetic high-density lipoprotein (sHDL) as a mediator of platelet activation, where it was
internalized by platelets and inhibited platelet aggregation in vitro and inhibited thrombus growth in vivo.
Therefore, in this present study we will be further investigating the mechanisms of 12-HETrE in combination
with the sHDL nanocarriers in its interactions with platelets to prevent thrombosis. The successful completion
of this present study will provide robust mechanistic insight into how sHDL is able to improve 12-HETrE's
antiplatelet properties and where or not it will increase its affinity for the IP receptor.

## Key facts

- **NIH application ID:** 10474068
- **Project number:** 3R35GM131835-03S1
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** MICHAEL Allan HOLINSTAT
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $20,577
- **Award type:** 3
- **Project period:** 2019-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10474068

## Citation

> US National Institutes of Health, RePORTER application 10474068, 12-HETrE regulation of blood coagulation, hemostasis, and thrombosis (3R35GM131835-03S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10474068. Licensed CC0.

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