Pulsatile stretch stimulates endothelial PDGFB secretion to maintain arterial vascular smooth muscle
The endothelial cells (ECs) that line blood vessels are remarkably sensitive to mechanical force. Hemodynamic force impacts ECs in three dimensions: laminar shear stress, intraluminal pressure, and circumferential stretch. The magnitude of these forces in arteries is pulsatile in nature—a quality that is lost in veins. The role of pulsatility in shaping these vessels is not well understood. Here we examine loss of pulmonary arterial pulsatility following the Glenn surgery (surgical palliation of single ventricle congenital heart disease). Using cultured pulmonary arterial ECs, we define the transcriptional changes driven by pulsatility within each dimension. We identify pulsatile stretch as a critical stimulus for endothelial secretion of PDGFB—a known driver of vascular smooth muscle cell (VSMC) proliferation—and show that loss of arterial pulsatility in vivo leads to thinning of VSMCs. This work provides a mechanistic understanding of how arterial pulsatility maintains the structure that supports arterial hemodynamic force. Overall design: Human pulmonary artery endothelial cells (HPAECs) exposed to either static, pulsatile, or non-pulsatile conditions of flow, stretch, or pressure