Mining the stiffness-sensitive transcriptome in human vascular smooth muscle cells identifies long non-coding RNA stiffness regulators

Vascular extracellular matrix (ECM) stiffening is a risk factor for aortic and coronary artery disease. How matrix stiffening regulates the transcriptome profile of human aortic (Ao) and coronary (Co) vascular smooth muscle cells (VSMCs) is not well understood. Furthermore, the role of long non-coding RNAs (lncRNAs) in the cellular response to stiffening has never been explored. This study characterizes the stiffness-sensitive transcriptome of human Ao and Co VSMCs and identify potentially key lncRNA regulators of stiffness-dependent VSMC functions. Ao and Co VSMCs were cultured on hydrogel substrates mimicking physiologic and pathologic ECM stiffness. Total RNA-seq was performed to compare the stiffness-sensitive transcriptome profiles of Ao and Co VSMCs. Overall design: 4 unique sample types with 4 replicates (16 total samples). Donor-matched Aortic and Coronary VSMCs were serum starved for 48 hours, then cultured in serum containing media for 24 hours on both soft and stiff fibronectin coated hydrogel matrices.