Mechanical Response of a Calcified Plaque Model to Fluid Shear Force

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Abstract
Vascular calcification is associated with atherosclerosis, but whether it mechanically affects plaque stability remains controversial. To assess the effect of mineralization on plaque vulnerability to mechanical shear stress, we applied fluid shear to cultures of calcifying vascular cells (CVC), a subpopulation of smooth muscle cells that spontaneously mineralize. CVC cultures containing nodules were treated for 10 days with vehicle control or beta-glycerophosphate (BGP) to accelerate mineralization. Cultures were placed in a parallel-plate flow system and were subjected to increasing fluid shear stress (4.9 dyn/cm2/min up to 400 dyn/cm2). The number of nodules remaining attached was recorded every 10 min. Results showed that control cultures and BGP-treated cultures, which contained significantly greater calcium mineral than control cultures, had similar detachment thresholds (50–100 dyn/cm2), with linear portions of their stress/detachment curves from 100 to 275 dyn/cm2. Based on repeated measure analysis of variance, BGP-treated nodules were no more likely to detach at a given shear than controls, although they showed a trend toward greater stability. Thus, calcification does not appear to increase plaque vulnerability to fluid shear stress, although it may contribute to a slight stabilization. This model may represent the first in vitro model of mechanical rupture of atherosclerotic plaque.