Biomechanics of Plaque Rupture and Cardiovascular Calcification

The rupture of an atheroma cap can lead to the formation of a thrombus, followed by a myocardial infarction. The development of atherosclerotic plaque vulnerable to rupture results from complex interactions among systemic, biological, and biomechanical factors. During pulsatile blood flow, the arterial wall experiences various mechanical stresses, including wall shear stresses (WSS) and vessel wall stresses. The ultimate stress needed to cause cap rupture is about five orders of magnitude greater than physiological WSS. Therefore, physiological or elevated WSS cannot cause rupture of the atheroma cap. However, WSS is crucial for the formation and progression of atheroma as well as the development of high-vulnerability traits within the atheroma. In turn, the ultimate tensile stress in the cap tissue depends on several factors, including the morphology, tissue composition, and the biochemical and biological environment of the atheroma. Key factors that increase stress in the vessel wall include a positively remodeled atheroma with low stenosis, containing soft, large lipid or necrotic pools, and a thin fibrous cap. The ultimate tensile stress of the cap tissue also depends on collagen content and crosslinking, increased macrophage numbers, matrix metalloproteinases secretion, chronic inflammation, smooth muscle cell apoptosis, neovascularization, intraplaque hemorrhage, coagulation factors, and the development of microcalcifications in the cap. The complex interaction between these factors can result in vessel wall stresses exceeding the ultimate stress threshold and leading to atheroma cap rupture. The role of calcification on the biomechanics of the atheroma and, in particular, the role of microcalcifications in increasing the risk of cap rupture are summarized. Overall, understanding the complex interplay of morphology, composition, and biological environment in the atheroma is essential for advancing our understanding of plaque rupture.