Myocardin Attenuates Aortic Aneurysm and Dissection Through the Maintenance of VSMC Homeostasis

Myocardin (Myocd) plays an important role in the maintenance and homeostasis of the vasculature. The loss of Myocd results in vascular smooth muscle cell (VSMC) phenotypic transition and thoracic aortic aneurysms and dissections (TAADs) by downregulating VSMC contractile genes. VSMC phenotypic transition plays a key role in the formation of abdominal aortic aneurysms and dissections (AAADs). However, little is known about the role of Myocd in AAAD. The effect of Myocd on AAA formation was proven in an angiotensin II (Ang II)-induced AAD model. Myocd overexpression or knockdown was achieved by the injection of the corresponding adeno-associated virus serotype 9 (AAV9) through the tail vein. The knockdown of Myocd in C57BL/6J mice treated with angiotensin II promoted the formation of AAAD, as demonstrated by increases in the maximal aortic diameter, vascular inflammation and elastin degradation relative to the control group, while Myocd-overexpressing ApoE-/- mice infused with Ang II were less likely to develop AAAD. Mechanistically, Myocd deficiency significantly repressed VSMC marker gene expression. In addition, qPCR results showed that Myocd knockdown promoted the expression of lncRNAs, which showed increased levels in human AAD tissues. Our results indicated the pivotal role of Myocd in protecting against AAAD formation. In this study, mouse aortic vascular smooth muscle cells (VSMCs) were isolated and transfected with adenoviruses for knockdown of Myocd. RNA-seq was performed on Myocd knockdown VSMCs and wildtype VSMCs.