# Fibrin(ogen) in Abdominal Aortic Aneurysm Pathogenesis

> **NIH NIH F31** · UNIVERSITY OF CINCINNATI · 2021 · $7,611

## Abstract

PROJECT SUMMARY/ABSTRACT
 Abdominal Aortic Aneurysm (AAA) results in significant morbidity and mortality in upwards to 15,000
patients in the United States. No effective pharmaceutical intervention exists and treatment is limited to surgical
intervention at the point of maximal expansion. The pathogenesis of this disease is poorly understood, making
development of pharmaceutical intervention difficult. The protein fibrinogen, an important participant in
hemostatic, inflammatory and wound-healing processes, is known to be elevated in AAA patients. However, this
observation has not been adequately investigated, and no mechanism to explain this elevation has been
experimentally identified. Work performed in our lab has demonstrated that depletion of fibrinogen in a mouse
model successfully attenuates an accepted animal model of AAA, and decreases inflammatory cytokines.
However, the molecular mechanism(s) responsible for fibrinogen mediated AAA pathogenesis remains unclear.
As such, understanding the molecular mechanism(s) responsible for fibrinogen depletion attenuating AAA could
lead to novel therapeutic strategies in AAA.
 The primary goal of this proposal is investigate the mechanisms by which fibrinogen contributes to AAA
pathogenesis. Specifically, we will study how macrophage binding with fibrinogen contributes to AAA
pathogenesis, and how fibrin clot structure and accompanying fibrinolytic resistance contributes to AAA
pathogenesis. We hypothesize that fibrinogen deposition into AAA accelerates aneurysmal growth by
increasing the activation of coagulation and inflammation. This hypothesis will be addressed with two
specific aims and several unique mouse models. In these aims, we will assess the influence of fibrinogen on
AAA through hemostatic action via analysis of fibrin clot structure and factor XIII (FXIII; aim 1) and
inflammatory action via deletion of the macrophage binding site in the fibrinogen gamma chain (aim 2). The
long term objective of this work is to identify a role for fibrinogen in this disease process. If successfully
completed, identified a mechanism to explain fibrinogen elevation in AAA patients. The outcomes from the
proposed studies are expected to have also significantly advanced our current knowledge of AAA
pathogenesis, and have a positive impact on our ability to identify possible targets for AAA therapy. This
fellowship grant will also train the principle investigator in molecular biology and functional genomics in order to
establish a research career in the field.

## Key facts

- **NIH application ID:** 10244953
- **Project number:** 5F31HL143987-04
- **Recipient organization:** UNIVERSITY OF CINCINNATI
- **Principal Investigator:** Hannah Russell
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $7,611
- **Award type:** 5
- **Project period:** 2018-09-01 → 2021-12-16

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10244953

## Citation

> US National Institutes of Health, RePORTER application 10244953, Fibrin(ogen) in Abdominal Aortic Aneurysm Pathogenesis (5F31HL143987-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10244953. Licensed CC0.

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