# Characterization of Coagulation Factor-platelet Interactions: Role of FXI

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2020 · $695,571

## Abstract

Project Summary:
Atherosclerosis remains the underlying cause of the majority of cardiovascular diseases contributing to
mortality. Our overall hypothesis is that pathological activation of two blood contact system proteins, factor
(F) XI and FXII, mediate platelet-endothelial interactions to promote inflammation and leukocyte trafficking
in experimental models of atherosclerotic plaque formation. Our preliminary studies linking contact
activation to inflammation and platelet activation suggest that pharmacological targeting of FXI could
reduce vascular inflammation, atherogenesis, and its cardiovascular complications, and would be safer
than traditional anticoagulants or platelet inhibitors, which carry a significant risk of fatal bleeding.
Our work and findings to date have opened the window towards the development of safer antithrombotic
strategies. This program will take a new direction to study whether contact activation increases platelet-
endothelial cell interactions, leukocyte recruitment and infiltration, and inflammation to promote
atherosclerotic plaque formation. This program will build on our ability to develop tools for molecular
imaging of cell interactions, the creation of novel inhibitors of contact activation, and rational and
responsible use of and translation from in vitro studies to in vivo mouse and non-human primate models of
disease. In Aim 1 we will determine the role of FXI in activating platelets to promote atherogenesis. We will
test our hypothesis that FXI-dependent platelet activation promotes recruitment of leukocytes to inflamed
endothelium. In Aim 2 we will determine the role of FXII in promoting inflammation in atherogenesis. We
will test our hypothesis that FXII activation of and by FXI induces cytokine and complement generation
that contribute to inflammation to promote atherogenesis. We will translate our mechanistic in vitro studies
to define the pathological role of contact activation in 2 distinct animal models of atherogenesis.
The translational relevance of our project will be the potential identification of safe molecular targets and
mechanisms that could support the development of novel pharmacological approaches to address the
problem of progressive atherosclerosis.

## Key facts

- **NIH application ID:** 9928074
- **Project number:** 5R01HL101972-11
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Owen J McCarty
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $695,571
- **Award type:** 5
- **Project period:** 2010-07-15 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9928074

## Citation

> US National Institutes of Health, RePORTER application 9928074, Characterization of Coagulation Factor-platelet Interactions: Role of FXI (5R01HL101972-11). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9928074. Licensed CC0.

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