Recent Advances in Molecularly Targeted Therapies for Atherosclerosis: From Pathophysiology to Clinical Application

Atherosclerosis is a complex chronic vascular disease characterized by lipid accumulation, persistent inflammation, endothelial dysfunction, and progressive structural remodeling of the arterial wall, underscoring the pathological basis of most cardiovascular diseases.Although statin-based lipid-lowering therapy has substantially reduced cardiovascular morbidity and mortality, a significant proportion of patients continue to experience residual lipid and inflammatory risks despite optimal treatment.These limitations have prompted a paradigm shift toward therapeutic strategies that directly target key molecular and cellular pathways underlying atherosclerotic pathophysiology.This review provides a comprehensive overview of the cellular and molecular mechanisms involved in the initiation and progression of atherosclerosis, including endothelial dysfunction, immune cell activation, and smooth muscle cell phenotypic modulation.Furthermore, this paper systematically summarizes current molecularly targeted therapeutic approaches in clinical use, encompassing low-density lipoprotein cholesterol-modifying agents, inflammation-targeting therapies, and lipoprotein(a)-directed interventions.Emerging strategies, such as RNA-based therapeutics and gene-editing technologies, are also discussed in the context of their mechanistic rationale and translational potential.By integrating the mechanistic insights with available clinical evidence, this review highlights the therapeutic benefits and limitations of current treatments and emphasizes the future directions toward precision and personalized strategies for preventing and managing atherosclerotic cardiovascular disease.