Fluid Shear Stress Destabilizes the Vascular Mesenchymal Stem Cells‐Derived Calcifying Nodules

Abstract

Calcification affects mechanical properties of atherosclerotic plaque. Whether it alters plaque vulnerability to rupture is controversial. To test effects of calcification on plaque stability under fluid shear, we used calcifying vascular cells (CVC), a subpopulation of smooth muscle cells that produce plaque-like nodules that calcify in the presence of beta-glycerophosphate (BGP). We applied ramp increases in fluid shear (0 - 400 dyn/cm2) to control and BGP-treated cultures placed in a modified parallel plate flow system. The number of nodules was recorded initially under static conditions and every 10minutes as shear stress was increased. The nodule detachment rate was quantified as the percentage of the nodules remaining attached in response to an incremental increase in shear stress. Results: Time-lapse photography captured the process of nodule destabilization and detachment. The detachment threshold was similar (50–100 dyn/cm2) for both control and BGP-treated nodules. The number of nodules remaining attached decreased almost linearly with shear stress above the detachment threshold. The rate of nodule detachment was not significantly different between the two groups (p>0.05, n=3), although there was a trend toward lower detachment rate in the BGP-treated nodules. Thus, calcified nodules show a trend toward resistance to fluid shear stress in vitro. This model may serve as a basis to understand the effects of calcification on vascular plaque rupture.