The natural evolution of human atherosclerosis involves the progression to a vulnerable state and rupture, a pathologic fate that is exclusive to humans.[1–6] Atherosclerosis growth and progression are spatial processes influenced by disturbed patterns of blood flow. The consequent vascular tissue disorganization corresponds to histologic patterns with regional distributions that are an integral part of histopathologic plaque classification.[2]
A vulnerable and prone-to-rupture plaque is traditionally characterized by a large necrotic core, a thin fibrotic cap, an inflammatory phenotype, and intraplaque hemorrhage.[1,5] These pathologic features and their unique spatial distribution in the tissue context contribute to the highly heterogeneous nature of atherosclerotic tissue.
In this issue of the Journal of the American College of Cardiology, Sun et al[7] use an integrated approach to perform an in-depth regional mapping of a total of 163 human atherosclerotic lesions to establish the anatomic coordinates of plaque rupture and identify the corresponding biochemical, cellular, and transcriptional changes along the regional flow direction.
Leveraging the Carotid Plaque Imaging Project (CPIP),[8]the researchers first performed a systematic analysis of 41 carotid endarterectomy specimens from symptomatic patients, dividing them into 3 regions: proximal, most stenotic, and distal. The exact site of rupture was consistently identified proximally or near to the most stenotic region at a median distance of 9 mm from the proximal plaque end.
