# Microvascular Thrombosis in systemic inflammation

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2022 · $375,236

## Abstract

Disseminated intravascular coagulation (DIC) is manifested in 25-50% of septic patients.
DIC can cause microvascular thrombosis, which leads to multiple organ dysfunction
syndrome (MODS) and death. Although significant progress has been made during the
past decade in sepsis management, sepsis mortality remains high (>30% mortality) and
is greater in patients with sepsis-induced MODS. Currently, there is no treatment for
sepsis-induced DIC. During the present funding period, we have developed a porcine
model for bacteria-induced DIC using a clinically relevant Methicillin-Resistant
Staphylococcus aureus (MRSA) strain. These animals were studied for up to 70 hours.
By using this novel lengthen porcine model, we observed a marked increment in
peripheral blood circulating vimentin (namely plasma Vim) after the intravenous
inoculation of the bacteria. This intriguing finding in septic pigs confirmed proteomics
studies that showed increased plasma Vim levels in septic human patients. These studies
validated the similarity of disease progression in pigs and humans. During signal
transduction studies in porcine model, we observed that MRSA insult elevated pro-
inflammatory signaling, increased serine phosphorylated plasma Vim levels and
decreased the activity of protein phosphatase 2A. Moreover, our studies showed that
exogenous Vim potentiated thrombin-induced fibrin polymerization, a process that can
contribute to microvascular thrombosis and coagulopathy in sepsis-induced DIC. The
goal of this project is to use human septic plasma and bacteria-induced systemic
inflammation model in pigs and investigate the potential mechanistic role for plasma Vim
in coagulopathy and in promoting pro-inflammatory signaling. We will employ a multi-PI
approach and propose three aims: Aim 1 will characterize structural features and activity
of plasma vimentin and determine how it contributes to coagulopathy. Aim 2 will
interrogate the function of plasma Vim in pro-inflammatory signaling during bacteria-
induced systemic inflammation. Aim 3 will investigate the role of plasma Vim in sepsis-
induced DIC using bacterial sepsis porcine model and human sepsis subjects. Successful
completion of these studies will reveal new mechanisms for the increased plasma Vim in
promoting microvascular thrombosis and pro-inflammatory signaling. The study has the
potential to identify plasma Vim as a new indicator and therapeutic target for sepsis-
induced DIC.

## Key facts

- **NIH application ID:** 10440455
- **Project number:** 5R01GM112806-08
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Miguel Angel Cruz
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $375,236
- **Award type:** 5
- **Project period:** 2014-09-25 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10440455

## Citation

> US National Institutes of Health, RePORTER application 10440455, Microvascular Thrombosis in systemic inflammation (5R01GM112806-08). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10440455. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*