CCN2 deficiency in smooth muscle cells triggers cell reprogramming and aggravates aneurysm development. CCN2 deficiency in smooth muscle cells triggers cell reprogramming and aggravates aneurysm development

Vascular smooth muscle cell (VSMC) phenotypic switching is widely recognized as a key mechanism responsible for the pathogenesis of several aortic diseases such as aortic aneurysm. Cellular communication network factor 2 (CCN2), often upregulated in human pathologies and animal disease models, exerts a myriad of context-dependent biological functions. However, current understanding of the role of SMC-CCN2 in SMC phenotypic switching and its function in the pathology of abdominal aortic aneurysm (AAA) is lacking. Here we report the effect of SMC-restricted CCN2 deficiency of hypercholesterolemic mice on gene expression in infrarenal aorta with or without angiotensin II (Ang II)-infusion. Overall design: CCN2-floxed mice were crossed with Myh11-Cre-ERT2 transgenic mice to generate male CCN2-floxed mice harboring SMC-specific Cre (CCN2fl/fl-Myh11-Cre-ERT2). Smooth muscle cell (SMC)-specific deletion of CCN2 was achieved by intraperitoneal (IP) injection of five consecutive doses of tamoxifen to 8 weeks old male CCN2fl/fl-Myh11-Cre-ERT2 mice. Age-matched male CCN2-floxed mice without Cre expression subjected to the same tamoxifen regimen were used as controls. After two-week washout period, SMC-specific CCN2-knockout mice, henceforth CCN2SMC∆ mice and CCN2-floxed control mice, henceforth CCN2fl/fl mice were used for the modeling of AAA (Ang II infusion via mini-osmotic pumps at the dose of 500 ng/kg/min for 7 days)