Abstract Background The inability to detect heterogeneity of atherosclerosis (AS) significantly hampers the implementation of personalized treatments to prevent coronary heart disease. Methods Here we describe the proteomic characteristics of human coronary arteries based on 233 coronary artery specimens from normal coronary arteries, early-stage, and late-stage atherosclerosis. Differential proteomic analysis and molecular subtyping provide a molecular profile distinguishing early from late stages and depict the landscape of the progression of coronary atherosclerosis. Results Proteomics reveal that complement and coagulation cascades, extracellular matrix (ECM) organization, and inflammation are classical pathways involved in the onset as well as in the progression of AS. We performed molecular subtyping across all samples, categorizing them into five subtypes. Subtype 1 (S1) involves ECM, complement and coagulation cascades, and inflammation. S2 is associated with translation, RNA metabolism, and mitochondrial structure. S3 is linked to RNA metabolism and translation. S4 relates to myofibrils and Rho GTPase. S5 encompasses inflammation, complement and coagulation cascades, and ECM. Pseudo-temporal analysis revealed the severity of the condition was determined to range from mild to severe as S2, S4, S3, S5, and S1. Conclusions The ECM organization, complement, and coagulation cascades pathways are continuously dysregulated during the occurrence and progression of atherosclerosis (AS). However, early AS upregulates translation, RNA metabolism, and myofibril pathways and inflammation promote the further development of AS.
Xu et al. (2025) studied this question.