Biomedical and Chemical Engineering Research Seminar Series

Role of Survivin in Cellular Mechanotransduction
Presented by Yongho Bae, University at Buffalo

Arterial stiffness is a major risk factor for cardiovascular disease and is associated with the pathological behavior of vascular smooth muscle cells (VSMCs). To identify potential mediators of stiffness-induced responses, we analyzed microarray data from mouse femoral arteries and VSMCs cultured on soft and stiff hydrogels. Our analysis identified 80 genes that were differentially regulated in response to stiffness, with functional enrichment analysis revealing a link to cell cycle progression and proliferation. Of these genes, Survivin was found to be a potential mediator of stiffness-induced cell cycling and proliferation, in vivo and in vitro, as determined by gene network and pathway analyses, qPCR, and immunoblotting. Additionally, we observed that stiffness-mediated Survivin expression is dependent on the activation of focal adhesion kinase (FAK) and small GTPase Rac, providing a mechanistic understanding of how extracellular matrix stiffness regulates VSMC patho-physiology. Our findings suggest that Survivin plays a crucial role in regulating VSMC behavior in response to arterial stiffness and may provide a potential therapeutic target for the prevention of cardiovascular disease.