Effects of Extracellular Matrix Softening on Vascular Smooth Muscle Cell Dysfunction

Upregulation of synthetic phenotype-related genes is observed in vascular smooth muscle cells (VSMCs) cultured on soft matrix hydrogels.

• VSMCs can shift from a contractile to a synthetic phenotype, contributing to aortic disease.
• Mechanical signals, including extracellular matrix (ECM) stiffness, influence VSMC function.
• Softening of the ECM leads to the dedifferentiation of VSMCs, as indicated by the increased expression of genes associated with the synthetic phenotype.
• In vivo experiments show that treatment with the lysyl oxidase inhibitor β-aminopropionitrile monofumarate (BAPN) results in ECM softening and promotes VSMC phenotypic switching.
• Mice treated with BAPN exhibit severe aortic expansion and develop aortic dissection.

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