# Mechanisms of microvascular thrombosis in inflammation

> **NIH VA I01** · MICHAEL E DEBAKEY VA MEDICAL CENTER · 2024 · —

## Abstract

Thrombosis and inflammation (or thromboinflammation) are interrelated in a variety of illnesses
including sepsis or the body’s dysregulated response to an infection, and the novel Coronavirus
2019 (COVID-19). Sepsis is typically the most common individual admission diagnosis in
intensive care units in the VA system, although during certain weeks in 2020, COVID-19 was
by far the leading acute medicine admission diagnosis at our VA Medical Center and others
in the VA system. Despite advances in critical care medicine, sepsis and COVID-19 remain
as life-threatening conditions resulting in significant morbidity, mortality, and a high
economic burden in Veterans and non-Veterans worldwide. Both COVID-19 and sepsis are
associated with microvascular thrombosis and coagulopathy and in both conditions, the
severity of coagulopathy is associated with increased mortality rates. Thus, understanding
the mechanisms of microvascular thrombosis in systemic inflammation such as sepsis
and COVID-19, has major clinical significance to the VA health care system. Recent work
from our laboratory demonstrate that an extracellular form of a cytoplasmic intermediate protein
circulating in plasma, vimentin, plays important roles in experimental thrombosis, and mediates
fibrin polymerization in COVID-19 and in sepsis-induced coagulopathy. This application aims
to understand the role of plasma vimentin in thrombosis and fibrin polymerization in systemic
inflammation. Our central hypothesis is that plasma vimentin mediates microvascular
thrombosis in sepsis and COVID-19 via enhancing thrombin-induced fibrin polymerization.
Two aims are proposed: Aim 1 will determine the role of plasma vimentin on microvascular
thrombosis in mice and on fibrin polymerization in Veterans with COVID-19- and sepsis-induced
coagulopathy. Aim 2 will define the role of post-translational modifications of vimentin and its cell-
specific origin on microvascular thrombosis. Completion of the proposed experiments will broaden
our understanding of the links between inflammation and microvascular thrombosis in sepsis and
COVID-19, and will provide the basis for future work aimed at preventing microvascular
thrombosis in systemic inflammation. The long-term goal is to develop optimal therapeutic
approaches for patients with sepsis, COVID-19, and other diseases associated with
thromboinflammation.

## Key facts

- **NIH application ID:** 10873058
- **Project number:** 5I01BX002551-08
- **Recipient organization:** MICHAEL E DEBAKEY VA MEDICAL CENTER
- **Principal Investigator:** ROLANDO E RUMBAUT
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2016-04-01 → 2029-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10873058

## Citation

> US National Institutes of Health, RePORTER application 10873058, Mechanisms of microvascular thrombosis in inflammation (5I01BX002551-08). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10873058. Licensed CC0.

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