# Fibrin(ogen) Structure and Interactions

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 2024 · $595,327

## Abstract

PROJECT SUMMARY
Fibrinogen is a multifunctional plasma protein that, after conversion into polymeric fibrin, promotes
hemostasis and plays a pivotal role in various physiological and pathological processes, including wound
healing, thrombosis, atherogenesis, tumorigenesis, and more. Inflammation and angiogenesis are integral
parts of wound healing; however, in pathological settings, these two processes contribute to the development
of inflammation-related cardiovascular diseases and the progression of tumor growth and metastasis. Our
previous studies primarily focused on the newly discovered fibrin-VLDL receptor-dependent inflammatory
pathway, which promotes the transendothelial migration of leukocytes and, consequently, inflammation. In
these studies, we established the molecular mechanism underlying this pathway and hypothesized that the
fibrin-derived β15-42 fragment, which was shown to exhibit significant protective effects in numerous
inflammation-related animal models, inhibits this pathway by interacting with a putative receptor. Recently,
we discovered that endothelial N-cadherin is a novel receptor for fibrin. Our extensive preliminary data
suggest that N-cadherin is a putative receptor for β15-42, and the interaction of fibrin with this receptor
promotes angiogenesis. Based on these data and our previous findings, we propose to characterize the
novel fibrin-(N-cadherin) interaction and establish its role in fibrin-dependent inflammation and angiogenesis.
Specifically, we aim to establish the structural basis for the fibrin-(N-cadherin) interaction (Specific Aim 1),
test our hypothesis that N-cadherin is a putative receptor for the β15-42 fragment, whose interaction with this
receptor inhibits leukocyte transmigration (Specific Aim 2), and test our hypothesis that fibrin-(N-cadherin)
interaction triggers fibrin-dependent angiogenesis (Specific Aim 3). Additionally, we intend to design novel,
efficient inhibitors of the fibrin-(N-cadherin) interaction with potent anti-inflammatory and anti-angiogenic
properties. These inhibitors may be developed as potential therapeutics for treating fibrin-dependent
inflammatory disorders and angiogenesis-related tumorigenesis.

## Key facts

- **NIH application ID:** 10978630
- **Project number:** 2R01HL056051-22A1
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** LEONID V. MEDVED
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $595,327
- **Award type:** 2
- **Project period:** 1998-01-01 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10978630

## Citation

> US National Institutes of Health, RePORTER application 10978630, Fibrin(ogen) Structure and Interactions (2R01HL056051-22A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10978630. Licensed CC0.

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