# Role of vimentin in thrombosis and stroke

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2020 · $391,051

## Abstract

ABSTRACT
Adhesion of platelets to stimulated endothelium contributes to thrombotic events associated with
arterial thrombosis and ischemic stroke. Although anti-platelet agents have reduced unfavorable
outcomes, it is well appreciated that the risk for bleeding or recurrent thrombotic events persists.
The pathophysiological function of the protein von Willebrand factor (VWF) in arterial thrombosis
and stroke has been validated by experimental and clinical studies. VWF is important for
mediating the tethering of the flowing platelets over the surface-bound VWF that result in platelet
adhesion, activation, and aggregation – and ultimately occlusion of the vessel. Recently, we
described that vimentin expressed on the cell surface of platelets binds to VWF and contributes to
platelet adhesion at high shear stress. We also have shown that a recombinant A2 domain of
VWF (“A2 protein”) with binding activity for vimentin blocked the interaction between vimentin and
VWF. Additional experiments employing endothelial cells (ECs), which also express vimentin on
the cell surface, revealed that that A2 protein prevented the formation of ultra large (long) VWF
multimers or VWF strings on normal ECs and failed to interact with vimentin-deficient ECs.
Moreover, the large number of VWF strings observed at the endothelial surface of stimulated
cerebral arteries from wild type (WT) mice contrast to the significantly less strings seen on arteries
from vimentin deficient mice. These data demonstrate for the first time the presence of
hyperadhesive VWF strings in the cerebrovasculature and the potential for these strings in
cerebrovascular pathologies. Finally, injury-induced thrombus formation in distal middle cerebral
artery (MCA) and severity of ischemic stroke was reduced in Vim(-/-) compared to WT mice. The
central hypothesis of this application is that cell-surface expressed vimentin interacts with the A2
domain of VWF strings, thus contributing to anchoring of VWF strings to the stimulated
endothelium and attachment to circulating platelets. This application also proposes to test the
hypothesis that disrupting the vimentin/VWF interaction reduces thrombosis and further damage
during ischemic reperfusion. Three aims are proposed: Aim 1) Define the essential sites in
vimentin and VWF that are involved in the vimentin/VWF interaction on platelets and endothelial
cells; Aim 2) Determine the role of platelet and endothelial vimentin in thrombosis in vivo; and
Aim 3) Demonstrate therapeutic benefit of disrupting the vimentin-VWF interaction following
stroke. Completion of these aims will impact public health by demonstrating a novel receptor for
VWF, and will lay the foundation to test this new interaction as a therapeutic target to prevent
arterial thrombosis and treat ischemic stroke.

## Key facts

- **NIH application ID:** 9927689
- **Project number:** 5R01NS094280-05
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Miguel Angel Cruz
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $391,051
- **Award type:** 5
- **Project period:** 2016-09-01 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9927689

## Citation

> US National Institutes of Health, RePORTER application 9927689, Role of vimentin in thrombosis and stroke (5R01NS094280-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9927689. Licensed CC0.

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