Integrin α9β1 deficiency does not impact the development of atherosclerosis in mice

Heliyon. 2024 Feb 9;10(4):e25760. doi: 10.1016/j.heliyon.2024.e25760. eCollection 2024 Feb 29.ABSTRACTSushi, von Willebrand factor type A, EGF and pentraxin domain containing 1 (SVEP1) is an extracellular matrix protein that causally promotes cardiovascular disease in humans and mice. However, the receptor mediating the effect of SVEP1 on the development of disease remains unclear. We previously demonstrated that depleting either vascular smooth muscle cell (VSMC)- or myeloid cell-derived integrin α9β1, the first receptor that was identified to interact with SVEP1, did not phenocopy the disease-abrogating effect of depleting SVEP1. Due to its wide expression in tissues and cell types, here we extend this line of investigation to definitively determine if integrin α9β1 impacts the development of atherosclerosis. In a mouse model of atherosclerosis, we found that depleting integrin α9β1 in all cells did not alter plaque size or characteristics of plaque complexity when compared to wild type mice. Further, the significant SVEP1-mediated effects on increase in macrophage content and VSMC proliferation within the atherosclerotic plaque were not altered in animals lacking integrin α9β1. Together, these findings strongly suggest that integrin α9β1 is not responsible for mediating the SVEP1-induced promotion of atherosclerosis and support further studies aimed at characterizing other receptors whose interaction with SVEP1 may represent a therapeutically targetable interacti...
Source: Atherosclerosis - Category: Cardiology Authors: Source Type: research