# Mechanisms for Deep Vein Thrombosis following Stroke

> **NIH NIH R01** · LOUISIANA STATE UNIV HSC SHREVEPORT · 2022 · $448,689

## Abstract

Project Summary/Abstract
Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE) have
an immense impact on morbidity and mortality. Acute ischemic stroke and aging are considered significant risk
for developing life-threatening VTE events. While prophylactic anticoagulation reduces the rates of VTE in such
high-risk patients, they only prevent approximately half of the expected VTE events and are associated with
significant risk of bleeding, suggesting the critical need for novel and safe adjuvant treatments to reduce VTE
burden. In recent years, compelling evidence has emerged that implicates neutrophils in the initiation and
pathogenesis of deep vein thrombosis (DVT). In pilot studies, we found that stroke increases the risk of DVT,
both in mice and humans and integrin α9 is upregulated on neutrophils following stroke in humans and in mice
and it contributes to adhesion of neutrophils to the endothelium. We also observe that neutrophil specific α9-/-
mice were less susceptible to DVT. Our central hypothesis is that neutrophil integrin α9 promotes DVT in the
context of aging and stroke. The overall objective of the proposal is to evaluate the mechanisms by which
neutrophil integrin α9 promotes DVT while exploring its relevance and therapeutic potential in reducing
poststroke DVT. In aim 1, we will determine the mechanistic role of neutrophil integrin α9 in promoting DVT in
the context of stroke and aging. We will evaluate underlying molecular mechanisms that contributes to
poststroke neutrophil adhesion and DVT. For optimal scientific rigor and to ensure reproducibility of the results,
we will test this hypothesis considering age, sex and the presence and absence of ischemic stroke. We will use
clinically relevant models (filament/embolic stroke models and IVC stenosis models for DVT). In aim 2, we will
determine the translational impact of inhibiting integrin α9 on venous thrombosis. We will use well
characterized anti-integrin α9 antibody in mouse models. By utilizing whole blood samples from controls and
patients with ischemic stroke, we will determine in vitro effect of integrin α9 inhibition on magnitude of venous
thrombosis. This project will provide robust evidence that neutrophil integrin α9 promotes DVT in the context of
stroke and aging. A longer-term impact of the project will be facilitation of the development of anti-integrin α9
therapeutics that can be used in combination with current thromboprophylaxis regimens to reduce VTE burden
in such high-risk population.

## Key facts

- **NIH application ID:** 10443141
- **Project number:** 1R01HL158546-01A1
- **Recipient organization:** LOUISIANA STATE UNIV HSC SHREVEPORT
- **Principal Investigator:** Nirav Dhanesha
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $448,689
- **Award type:** 1
- **Project period:** 2022-08-20 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10443141

## Citation

> US National Institutes of Health, RePORTER application 10443141, Mechanisms for Deep Vein Thrombosis following Stroke (1R01HL158546-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10443141. Licensed CC0.

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