Abstract

Sushi, von Willebrand factor type A, EGF and pentraxin domain containing 1 (SVEP1) is a poorly understood, putative extracellular matrix protein. Several human traits and diseases are associated with SVEP1, including coronary artery disease, hypertension, type 2 diabetes, glaucoma, dementia, longevity, and platelet reactivity. This dissertation establishes a causal link between SVEP1 and human disease using Mendelian randomization and mouse models. It also provides insights into the disease mechanisms of the protein, including a novel interaction between SVEP1 and the orphan receptor Platelet endothelial aggregation receptor 1. The relevance of this interaction to platelet biology and its potential role in cardiometabolic disease is discussed. The viability of inhibiting SVEP1 to treat or prevent disease is also evaluated.

Committee Chair

Nathan O Stitziel

Committee Members

Carmen M Halabi, Robert P Mecham, Joel D Schilling, Amber N Stratman

Degree

Doctor of Philosophy (PhD)

Author's Department

Biology & Biomedical Sciences (Molecular Genetics & Genomics)

Author's School

Graduate School of Arts and Sciences

Document Type

Dissertation

Date of Award

2-25-2024

Language

English (en)

Author's ORCID

https://orcid.org/0000-0002-9612-7764

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