Atherosclerotic plaque phenotypes: Unraveling complexity and heterogeneity

Atherosclerosis is a localized form of specialized chronic inflammation, leading to thickening of the arterial wall due to the accumulation of lipids, cells, and connective tissue in the subendothelial space. The formation of an atherosclerotic plaque is a slow process that commonly starts early life and continues asymptomatically for many decades. However, several genetic or environmental risk factors can speed up this process and lead to cardiovascular events such as myocardial infarction and stroke or even to sudden death. The heterogeneity in cardiovascular risk/disease severity and related symptoms reflects a substantial heterogeneity in plaque composition, structure, and proneness to rupture or erosion. Therefore, a thorough understanding of the factors that may influence the lipid and cellular composition of an atheromatous plaque and its susceptibility to destabilization is paramount to the development of novel prognostic, diagnostic, and personalized therapeutic regimens that are urgently needed. In this chapter, we discuss the phenotypic characteristics of the atherosclerotic plaques, the clinical relevance of plaque phenotyping, and the mechanisms that contribute to plaque formation, progression, and stability.