The role of shear stress in the destabilization of vulnerable plaques and related therapeutic implications

American Heart Association type IV plaques consist of a lipid core covered by a fibrous cap, and develop at locations of eccentric low shear stress. Vascular remodelling initially preserves the lumen diameter while maintaining the low shear stress conditions that encourage plaque growth. When these plaques eventually startto intrude into the lumen, the shear stress in the area surrounding the plaque changes substantially, increasing tensile stress at the plaqueshoulders and exacerbating fissuring and thrombosis. Local biological effects induced by high shear stress can destabilize the caap, particularly on its upstream side, and turn it into a rupture-prone, vulnerable plaque. Tensile stress is the ultimate mechanical factor that precipitates rupture and atherothrombotic complications. The shear-stress-oriented view of plaque rupture has important therapeutic implications. In this review, we discuss the varying mechanobiologic mechanisms in the areas surrounding the plaque that might explain the otherwise paradoxical observations and unexpected outcomes of experimental therapies.