Ras-related protein 2 limits vascular smooth muscle cell phenotypic switching and abdominal aortic aneurysm development

Abdominal aortic aneurysm (AAA) and the attendant catastrophic event of rupture remain a leading cause of death. During AAA, VSMCs lost contractile-related phenotype, with reduced levels of actin alpha 2, smooth muscle (ACTA2), transgelin (TAGLN) and calponin 1 (CNN1)) , and obtain ability to secrete matrix metalloproteinases to degrade the extracellular matrix and weaken the arterial wall, which potentiate the rupture of the aneurysm. Angiotensin 2 (Ang II) can induce phenotype transition of VSMCs，while the underlying mechanism remains elusive. Here we found Ang II treatment could reduce expression of R-Ras2, thus reducing the phosphorylation and nuclear translocation of TFII-I, as a result, the gene expression of ACTA2, TAGLN and CNN1 were inhibited and VSMCs lost the contractile phenotype. RNA-seq profile of HASMCs stimulated with PBS or Ang II