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, Apoe-/- mice (single knockout, SKO) and Apoe-/- × Smtn-B-/- mice (double knockout, DKO) were subjected to an angiotensin II-induced AAA model for 28 days. AAA incidence, histopathological changes, and gene expression profiles were evaluated. AAA incidence was significantly lower in the DKO group compared with the SKO group. Histological analysis demonstrated significantly reduced Alcian blue-positive and Mac-2-positive areas 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. Immunohistochemical analysis further demonstrated that the S100A4-positive area was significantly reduced in the DKO group, consistent with the mRNA expression results. 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 SMC phenotype during AAA pathogenesis.