Human coronary atherosclerosis: biological insights and implications for prevention

Early human coronary atherosclerosis as coordinated biological reprogramming. Schematic illustrating a conceptual framework derived from integrated histopathological and multi-omic analyses of human coronary arteries. Normal coronary arteries in young adults display intact endothelial function, quiescent smooth muscle cells, and balanced cellular metabolism. During the earliest preclinical stages of atherogenesis, the vessel wall undergoes coordinated biological reprogramming, characterised by alterations in metabolic pathways and mitochondrial function, and regulatory signalling networks orchestrated by hierarchical molecular regulators (e.g. MLXIPL). These changes occur before overt inflammatory cell infiltration or significant luminal narrowing. Progression is marked by early lesion biology, including endothelial activation, extracellular matrix remodelling, and smooth muscle cell phenotypic modulation. Collectively, these insights underscore the importance of early and sustained risk-factor control to modify fundamental disease biology.