Phenotypic plasticity of vascular smooth muscle cells in aortic dissection: Insights from ex vivo flow exposure studies

Abstract

Aortic dissection Stanford type B cases often see false lumen enlargement, leading to severe complications. This study hypothesizes that in chronic aortic dissection, upon exposure to blood flow, vascular smooth muscle cells (VSMCs) switch their phenotype to be synthetic, increasing the production of matrix metalloproteinases (MMPs) that degrade the extracellular matrix (ECM) and weaken the false lumen wall, leading to the false lumen enlargement. Male Sprague-Dawley rats’ aortas, with endothelial cells removed, were incubated under flow-loading conditions in a specialized ex vivo system for 48 hours to test this hypothesis. Viability assays confirmed that VSMCs remained largely viable post-incubation. Gene expression analysis revealed a decrease in the contractile phenotype but no change in the synthetic phenotype, with no differences due to the wall shear stress (WSS) value. MMP-2 and MMP-9 expression changed after the incubation, but no remarkable difference was detected for the WSS value. Elastin structure remained unchanged, indicating no ECM degradation during the incubation period. These results suggest that ex vivo incubation does induce phenotype change in VSMCs, but direct flow on VSMCs might not lead to further phenotype changes or MMP production within 48 hours. Potential reasons include the presence of the internal elastic lamina preventing direct WSS on VSMCs or the short incubation duration. This study underscores the complexity of VSMC phenotype switching and its role in vascular diseases, advocating for more nuanced analysis and advanced techniques to unravel the mechanisms of false lumen enlargement in aortic dissection.