Overstretch causes lipid accumulation in vascular smooth muscle cells dependent on NADPH oxidase 1.

At the bend and bifurcation of arteries prone to atherosclerosis, pulsatile blood retention may cause overstretch on the tube wall. It has been reported that more than half of the foam cells found in atherosclerotic plaques are derived from vascular smooth muscle cells (VSMCs), but the mechanism is not adequately understood. In this work, we used a microfluidic device to apply a cyclic stretch (15 ​% and 0.05 ​Hz) on the VSMC for 24 ​h. The stretch caused a significant increase in the intracellular lipid accumulation, accompanying with the increased NOX1 and CD36 protein expression. On the other hand, inhibition of NOX1 activity, elimination of reactive oxygen species (ROS), or knockdown of NOX1 expression could significantly inhibit intracellular lipid accumulation. In addition, the NOX1 upregulation caused by 15 ​% stretch was related to the JAK/STAT signaling pathway. Our results reveal a novel mechanism of VSMC foam cell formation caused by the upregulation of NOX1.