# Fibrin(ogen) Structure and Interactions

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 2021 · $460,850

## Abstract

SUMMARY
Fibrinogen is a multifunctional plasma protein that after conversion into fibrin promotes hemostasis and
contributes to other physiological and pathological processes including inflammation, which plays a pivotal
role in the pathophysiology of cardiovascular diseases. Recruitment of leukocytes from the circulation to
sites of inflammation is an integral part of the inflammatory response and transendothelial migration of
leukocytes is a key step in such recruitment. Our previous study revealed that fibrin interacts with the VLDL
receptor (VLDLR) on endothelial cells and this interaction promotes leukocyte transmigration and thereby
inflammation. Further, we clarified the molecular mechanism of fibrin-VLDLR interaction and identified two
anti-VLDLR monoclonal antibodies that inhibit this interaction, and exhibit significant anti-inflammatory
properties and cardioprotective effects in animal models. Thus, fibrin-VLDLR interaction triggers a novel
fibrin-VLDLR-dependent pathway of leukocyte transmigration, which may contribute to the pathophysiology
of myocardial ischemia-reperfusion injury. However, the molecular mechanism underlying this pathway is
still unclear. We have generated numerous preliminary data that indicate the feasibility of studying this
interaction by NMR and suggest that there is a link between this pathway and VE-cadherin. Based on
these data we propose to solve NMR solution of a complex between fibrin- and VLDLR-derived fragments
and establish the structural basis for fibrin-VLDLR interaction (Specific Aim 1). Next, we will test our
hypothesis that fibrin promotes leukocyte transmigration by increasing endothelial permeability via a
VLDLR-dependent internalization of VE-cadherin (Specific Aim 2). Finally, we will test our new concept
related to the anti-inflammatory mechanism of fibrin-derived 15-42 peptide and will develop more efficient
anti-inflammatory agents (Specific Aim 3). Thus, the major goals of the proposed project are to establish
the molecular mechanisms underlying fibrin-dependent inflammation and, based on the results obtained, to
design more efficient anti-inflammatory agents that can be developed as novel therapeutics for treatment of
fibrin-dependent inflammatory disorders including myocardial ischemia-reperfusion injury.

## Key facts

- **NIH application ID:** 10167759
- **Project number:** 5R01HL056051-21
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** LEONID V. MEDVED
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $460,850
- **Award type:** 5
- **Project period:** 1998-01-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10167759

## Citation

> US National Institutes of Health, RePORTER application 10167759, Fibrin(ogen) Structure and Interactions (5R01HL056051-21). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10167759. Licensed CC0.

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