The role of Smoothelin-B in abdominal aortic aneurysm formation

Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease, and its underlying mechanisms remain incompletely understood. Vascular smooth muscle cells (SMCs) are the predominant cell type in the aortic wall, and SMC dysfunction contributes to AAA development and progression. Smoothelin-B (Smtn-B) is an actin-binding protein specifically expressed in fully differentiated, contractile SMCs and is essential for maintaining the contractile apparatus. However, its role in AAA pathogenesis has yet to be clarified. To investigate this, we generated Apoe -/- × Smtn-B -/- mice (Double knockout, DKO) by crossing Apoe -/- (single knockout, SKO) mice with Smtn-B -/- mice. At 10 weeks of age, both groups were infused with angiotensin II via subcutaneous osmotic pumps for 28 days. AAA incidence was assessed at 14 weeks of age. Histological evaluation included hematoxylin-eosin, alcian blue and immunohistochemistry for Mac-2 and SM-MHC. Real-time PCR was performed to analyze mRNA expressions of SM-MHC, α-SMA, SM-calponin, S100A4, F4/80, IL-6, MCP-1, Ccl5, TGF-β, and Col1a1. AAA incidence was significantly reduced in the DKO group as compared to the SKO group. Histological analysis showed that the areas stained positive with alcian blue and by Mac-2 immunohistochemistry were significantly smaller in DKO mice. Gene expression levels of S100A4, F4/80, MCP-1, Ccl5, TGF-β, and Col1a1 were also significantly decreased in the DKO group. Smtn-B deficiency may suppress AAA development by reducing macrophage infiltration and SMC phenotypic switching via MCP-1, Ccl5, and S100A4 downregulation. These findings suggest a novel role for Smtn-B in modulating vascular inflammation and SMCs phenotype during AAA pathogenesis.