| First Author | Jung IH | Year | 2022 |
| Journal | Atherosclerosis | Volume | 360 |
| Pages | 15-20 | PubMed ID | 36215801 |
| Mgi Jnum | J:330222 | Mgi Id | MGI:7366640 |
| Doi | 10.1016/j.atherosclerosis.2022.09.015 | Citation | Jung IH, et al. (2022) Vascular smooth muscle- and myeloid cell-derived integrin alpha9beta1 does not directly mediate the development of atherosclerosis in mice. Atherosclerosis 360:15-20 |
| abstractText | BACKGROUND AND AIMS: Sushi, von Willebrand factor type A, EGF pentraxin domain-containing 1 (SVEP1), an extracellular matrix protein, is a human coronary artery disease locus that promotes atherosclerosis. We previously demonstrated that SVEP1 induces vascular smooth muscle cell (VSMC) proliferation and an inflammatory phenotype in the arterial wall to enhance the development of atherosclerotic plaque. The only receptor known to interact with SVEP1 is integrin alpha9beta1, a cell surface receptor that is expressed by VSMCs and myeloid lineage-derived monocytes and macrophages. Our previous in vitro studies suggested that integrin alpha9beta1 was necessary for SVEP1-induced VSMC proliferation and inflammation; however, the underlying mechanisms mediated by integrin alpha9beta1 in these cell types during the development of atherosclerosis remain poorly understood. METHODS AND RESULTS: Here, using cell-specific gene targeting, we investigated the effects of the integrin alpha9beta1 receptor on VSMCs and myeloid cells in mouse models of atherosclerosis. Interestingly, we found that depleting integrin alpha9beta1 in either VSMCs or myeloid cells did not affect the formation or complexity of atherosclerotic plaque in vessels after either 8 or 16 weeks of high fat diet feeding. CONCLUSIONS: Our results indicate that integrin alpha9beta1 in these two cell types does not mediate the in vivo effect of SVEP1 in the development of atherosclerosis. Instead, our results suggest either the presence of other potential receptor(s) or alternative integrin alpha9beta1-expressing cell types responsible for SVEP1 induced signaling in the development of atherosclerosis. |
