# Role of Platelet Bruton's Tyrosine Kinase (BTK) in Atherosclerosis

> **NIH NIH F30** · OREGON HEALTH & SCIENCE UNIVERSITY · 2022 · $51,752

## Abstract

Project Summary
Atherosclerosis is the leading cause of cardiovascular disease, accounting for nearly 30% (859,125) of deaths
in the United States, with an estimated direct healthcare cost of $218.7 billion every year. Patients with late
stage atherosclerosis suffer from life-threatening complications, such as myocardial infarctions, ischemic
strokes, aneurysms, and multi-organ failure. Many current treatment options, such as anti-platelet and anti-
coagulant therapies, although successfully alleviating or preventing thrombotic events of atherosclerosis, carry
a risk for bleeding and hemorrhagic complications. Thus, there is a clear need to further understand the
molecular basis of hemostasis and thrombosis in order develop safer and more effective therapies.
In this regard, one recent therapeutic group of interest is tyrosine kinase inhibitors (TKIs). Tyrosine kinase
inhibitors targeting Bruton’s tyrosine kinase (BTK), including ibrutinib, have traditionally been used with great
success in treating hematological malignancies, such as chronic lymphocytic leukemia (CLL), and
inflammatory conditions, such as rheumatoid arthritis. Due to the central role of BTK also seen in platelet
activation, BTK inhibitors have recently been studied as a potential anti-platelet agent, demonstrating effects
against atherosclerotic plaque-triggered thrombus formation; however, the mechanisms by which platelet BTK
is activated and its functional effects remain largely ill-defined.
To this end, our proposal aims to characterize in platelets the regulation of BTK (Aim 1) and functional effects
of BTK (Aim 2) in atherosclerosis, to reduce thrombotic complications while minimally affecting hemostasis. To
investigate the role of platelet BTK in atherosclerosis, 1) we will bring together for the first time physiological
and phosphoproteomics methods to perform a combinatorial analysis delineating the regulatory signaling
cascades that activate BTK in platelets; and 2) we will define the effects of BTK activation on platelet functional
responses and investigate the interplay between platelets, endothelial cells, and leukocytes classically seen at
the microenvironment of atherosclerotic plaque rupture.
The potential translational relevance of our project will be the identification of safe and druggable molecular
target and mechanisms within the platelet activation pathway. Our research may ultimately provide rationale for
the development and use of classic BTK inhibitors as secondary anti-platelet and anti-thrombotic agents that
could safely benefit patients who suffer from atherosclerosis and its complications.

## Key facts

- **NIH application ID:** 10549282
- **Project number:** 5F30HL158079-02
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Tony Zheng
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $51,752
- **Award type:** 5
- **Project period:** 2021-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10549282

## Citation

> US National Institutes of Health, RePORTER application 10549282, Role of Platelet Bruton's Tyrosine Kinase (BTK) in Atherosclerosis (5F30HL158079-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10549282. Licensed CC0.

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