# Role of glycosaminoglycans (GAGs) in deep vein thrombus formation and resolution

> **NIH NIH F30** · OREGON HEALTH & SCIENCE UNIVERSITY · 2022 · $51,752

## Abstract

PROJECT SUMMARY
Venous thromboembolism disorders represent the third most common cause of death from cardiovascular
disease. Despite the addition of catheter directed thrombolysis to standard anticoagulation therapy, recurrent
deep vein thrombosis (DVT) and subsequent post-thrombotic-syndrome (PTS), where the signs and symptoms
of DVT persist or worsen with thrombus resolution, still cause long term disability. Thus, a better understanding
of the basic mechanisms of DVT formation and resolution is needed.
In order for a DVT to form, endothelial cell (EC) injury must occur. Recently, the EC glycocalyx (eGCX), a
membrane bound mesh of glycoproteins, proteoglycans, and associated glycosaminoglycans (GAGs), has come
into focus as a multifunctional surface layer capable of regulating vasodilation, inflammation, proliferation, and
coagulation pathways. The 3 most prominent eGCX GAGs, heparan sulfate (HS), chondroitin sulfate (CS), and
hyaluronan (HA), have been associated with binding sites for anti-thrombin, heparin cofactor II, and non-
circulating factor XI (FXI). GAG binding of these critical coagulation components suggests an ambiguous
and currently unclarified role for GAGs in thrombus formation and resolution, warranting further
mechanistic investigation.
The goal of this proposal is to elucidate the mechanistic role by which the eGCX regulates DVT formation and
resolution. My hypothesis maintains that an injured eGCX will bolster DVT formation by increasing platelet-EC
interactions and activating the intrinsic clotting pathway, via release of non-circulating FXI. Furthermore, the
injured eGCX will impair DVT resolution by increasing inflammatory (M1) monocyte infiltration into the thrombus
and the vein wall. In Aim 1, I will determine the role of eGCX GAGs in platelet activation and thrombus formation
using a caval constriction DVT model in wildtype CD1 mice. In Aim 2, I will determine the role of eGCX GAGs
in causing post-thrombotic vein wall changes. This study will potentially identify relevant therapeutic targets that
directly affect DVT formation and resolution, paving the way for interventional studies and supporting the
rationale for the development of selective, safe, and effective antithrombotic agents. These studies will be
performed at Oregon's primary academic medical center, the Oregon Health and Science University in the
Departments of Biomedical Engineering and Vascular Surgery under the co-mentorship of Dr. Monica Hinds,
PhD and Dr. Khanh Nguyen, MD. The PI is supported by a mentorship team of senior scientists and physicians
with expertise in vascular pathophysiology, thrombosis, and vascular surgery. Career development activities
include training in mouse surgery, in vitro and in vivo analysis techniques, and coagulation and vascular
pathophysiology, as well as training in communication and leadership skills. This training is designed to support
the PI's career goals of becoming a physician-scientist with a long-term career go...

## Key facts

- **NIH application ID:** 10463067
- **Project number:** 1F30HL163918-01
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Rick Mathews
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $51,752
- **Award type:** 1
- **Project period:** 2022-07-27 → 2026-07-26

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10463067

## Citation

> US National Institutes of Health, RePORTER application 10463067, Role of glycosaminoglycans (GAGs) in deep vein thrombus formation and resolution (1F30HL163918-01). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10463067. Licensed CC0.

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