Shear stress and advanced atherosclerosis in human coronary arteries.

The role of low and oscillating shear stress as a key factor for localizing early atherosclerotic plaques is generally accepted. Once more advanced plaques protrude into the lumen, the shear stress they are exposed to changes. The influence of shear stress on plaque composition in advanced atherosclerosis is not fully understood. In this review, we discuss our recent studies on the relationship between shear stress and plaque composition and the location of plaque rupture in human coronary arteries. We have shown that elevated shear stress levels can be found over plaques inducing only mild luminal narrowing and are not subjected to treatment. Regional exposure of certain plaque regions to high shear stress is therefore a condition that will pertain for a prolonged period of time. We have also shown that in more advanced atherosclerosis the necrotic core experiences higher shear stress. Low shear stress plaque regions can be found downstream of the plaque and are stiffer. High shear stress plaque regions can be found either at the upstream, shoulder or cap region of the plaque and are softer. The plaque regions with the highest strain levels are the regions that are exposed to the highest shear stress. The high shear stress plaque regions are the only plaque regions that get softer over time. Finally, high shear stress is also associated with the location of plaque rupture in non-culprit lesion in human coronary arteries. Combining our findings with data from literature, we can conclude that advanced coronary plaques grow in the distal regions. The distal plaque regions are exposed to low shear stress, are stiffer and have a stable plaque phenotype. The regions exposed to high shear stress are softer, and are associated with vulnerable plaque features.