调脂药物研究现状及研发前景OA

Dyslipidemia is a core driver for atherosclerotic cardiovascular disease(ASCVD),participating in the development of metabolic dysfunction-associated steatohepatitis(MASH),type 2 diabetes mellitus,obesity,and related malignancies through multiple mechanisms,including lipotoxicity,inflammatory activation and immunometabolic remodeling.According to the 2024 China Cardiovascular Health and Disease Report,the prevalence of dyslipidemia among adults in China is as high as 38.1％,contributing to a sustained increase in the burden of ASCVD.Although statins significantly reduce the risk of ASCVD events,the problems of residual cardiovascular risk and intolerance remain.In recent years,rapid advances have been made in monoclonal antibodies,antisense oligonucleotides,and RNA interference technologies targeting key molecules such as PCSK9,ANGPTL3,apo C3,and Lp(a),which brings new breakthroughs in the development of lipid-modifying agents.Beyond cardiovascular disease,targeting lipid metabolism has emerged as a promising therapeutic strategy for MASH and cancer.The THRβ,GLP-1R have emerged as important novel targets for the treatment of MASH and related disease.Collectively,lipid-modifying therapy is undergoing a paradigm shift from simply lowering LDL-C to achieving systemic metabolic improvement.This review systematically outlines the current state of application and development of lipid-modifying drugs based on the mechanistic basis and clinical evidence,and offers perspectives on future directions of drug development from a preclinical viewpoint.