基于RNA疗法在动脉粥样硬化性心血管疾病血脂管理的研究进展  

RNA-Based Therapies in Lipid Management of Coronary Atherosclerotic Cardiovascular Disease

作　　者：王申仪 阳军[1] WANG Shenyi;YANG Jun(Department of Cardiology,The First Affiliated Hospital of Hunan Normal University,Changsha 410005,Hunan,China)

机构地区：[1]湖南师范大学第一附属医院心血管内科,湖南长沙410005

出　　处：《心血管病学进展》2021年第4期369-373,共5页Advances in Cardiovascular Diseases

基　　金：湖南省2016年卫计委科技创新项目投资计划资助项目(NO:B2016007);2019年湖南省研究生科研创新项目(CX20190407)。

摘　　要：血脂异常,如低密度脂蛋白胆固醇和甘油三酯升高或高密度脂蛋白胆固醇降低等,是动脉粥样硬化性心血管疾病发生和发展的重要危险因素。尽管他汀类药物是预防心血管疾病的主要药物,但依然存在心血管疾病残余风险。基于RNA的治疗可提供更有效的治疗选择。其优势在于药物靶向RNA的高度特异性区域,进而调节脂质和脂蛋白的代谢。目前,N-乙酰半乳糖胺结合RNA靶向药物抑制关键调节蛋白(如前蛋白转化酶枯草溶菌素9、载脂蛋白CⅢ、脂蛋白a和血管生成素样蛋白3)翻译,在血脂管理中显示出其独特的疗效,显著改善动脉粥样硬化性心血管疾病的预后。现对主要的靶向RNA治疗策略、目前临床研究现状和未来的前景进行综述。Dyslipidemia,such as low-density lipoprotein cholesterol,elevated triglyceride or decreased high-density lipoprotein cholesterol,is an important risk factor for the development of atherosclerotic cardiovascular disease.Although statins are the main drugs for the prevention of cardiovascular disease,there is still considerable residual risk remains.RNA-based therapies may offer more effective treatment options.The advantage of oligonucleotide-based treatments is that drug candidates are targeted at highly specific regions of RNA that code for proteins that in turn regulate lipid and lipoprotein metabolism.At present,N-acetylgalactosamine-conjugated RNA-targeting drugs to inhibit the translation of key regulatory proteins[such as PCSK9,apolipoprotein CⅢ,lipoprotein a and angiogenin-like factor 3]has been shown to be effective in attenuating dyslipidemic states and the cardiovascular prognosis is improved significantly.In this paper,the main strategies of targeted RNA therapy,current clinical research status and future prospects will be reviewed.

关 键 词：低密度脂蛋白胆固醇 前蛋白转化酶枯草溶菌素9 载脂蛋白CⅢ 脂蛋白a 血管生成素样蛋白3 RNA靶向疗法 

分 类 号：R54[医药卫生—心血管疾病]