Vascular smooth muscle- and myeloid cell-derived integrin α9β1 does not directly mediate the development of atherosclerosis in mice

Jung, In-Hyuk; Elenbaas, Jared S.; Burks, Kendall H.; Amrute, Junedh M.; Zhang, Xiangyu; Alisio, Arturo; Stitziel, Nathan O.

doi:10.1016/j.atherosclerosis.2022.09.015

Cited by 5 publications

(1 citation statement)

References 38 publications

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“…In fact, zebrafish Svep1 lacks the putative integrin α9β1 binding domain altogether 47 . Mice lacking Itga9 in monocytes and smooth muscle cells also fail to phenocopy the atherosclerosis phenotype of mice lacking Svep1 57 . These findings suggest that SVEP1 is likely to have additional interactions related to its role in development and disease.…”

Section: Discussionmentioning

confidence: 99%

SVEP1 is an endogenous ligand for the orphan receptor PEAR1

et al. 2023

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Sushi, von Willebrand factor type A, EGF and pentraxin domain containing 1 (SVEP1) is an extracellular matrix protein that causally promotes vascular disease and associates with platelet reactivity in humans. Here, using a human genomic and proteomic approach, we identify a high affinity, disease-relevant, and potentially targetable interaction between SVEP1 and the orphan receptor Platelet and Endothelial Aggregation Receptor 1 (PEAR1). This interaction promotes PEAR1 phosphorylation and disease associated AKT/mTOR signaling in vascular cells and platelets. Mice lacking SVEP1 have reduced platelet activation, and exogenous SVEP1 induces PEAR1-dependent activation of platelets. SVEP1 and PEAR1 causally and concordantly relate to platelet phenotypes and cardiovascular disease in humans, as determined by Mendelian Randomization. Targeting this receptor-ligand interaction may be a viable therapeutic strategy to treat or prevent cardiovascular and thrombotic disease.

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Section: Discussionmentioning

confidence: 99%