Department of Pharmacology and Toxicology, Faculty of Medicine, American University of Beirut, P.O. Box 11-0236, Beirut, Lebanon.
Department of Biology, College of Science, United Arab Emirates University, Al-Ain, P.O. Box 17551, United Arab Emirates.
Curr Med Chem. 2021;28(36):7427-7445. doi: 10.2174/0929867328666210222092628.
Cardiovascular disease (CVD) remains the primary cause of global morbidity and mortality. CVD includes various life-threatening conditions such as myocardial infarction, stroke and peripheral arterial diseases. In this context, atherosclerosis continues to play the principal role in the pathogenesis of these conditions. Atherosclerosis emanates from a set of modifiable and non-modifiable risk factors that include age, male gender, family history, obesity, smoking, diabetes mellitus and hypertension. Recent evidence classifies atherosclerosis as a latent disease affecting all-sized arteries with a predilection for arterial branching points of decreased or absent blood supply. Atherosclerosis is not only a lipid metabolism disorder, but is also a chronic inflammatory one. This review providesa synoptic discussion of the underlying pathological mechanisms of atherosclerosis andthe currently applied therapeutic interventions. We then discuss the classical lipid-lowering therapies as well as the newly discovered therapies. For the classical therapies, we point out the importance of statins and ezetimibe in reducing plasma cholesterol levels by virtue of their effects on synthesis, reuptake and intestinal absorption of cholesterol. We also discuss the role of fibrates in modulating lipid metabolism and improving the ratio of high-density to low-density density lipoproteins. This study focuseson the more recent molecular and genetic interventions exemplified by proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies, evinacumab, and microRNA inhibitors. Special attention is also given to clinical trials involving these therapies.
心血管疾病（CVD）仍然是全球发病率和死亡率的主要原因。CVD 包括各种危及生命的疾病，如心肌梗死、中风和外周动脉疾病。在这种情况下，动脉粥样硬化继续在这些疾病的发病机制中发挥主要作用。动脉粥样硬化源于一组可改变和不可改变的危险因素，包括年龄、男性、家族史、肥胖、吸烟、糖尿病和高血压。最近的证据将动脉粥样硬化归类为一种潜在的疾病，影响所有大小的动脉，偏爱血液供应减少或不存在的动脉分支点。动脉粥样硬化不仅是一种脂质代谢紊乱，也是一种慢性炎症。本综述全面讨论了动脉粥样硬化的潜在病理机制和目前应用的治疗干预措施。然后我们讨论了经典的降脂治疗方法以及新发现的治疗方法。对于经典的治疗方法，我们指出他汀类药物和依折麦布通过影响胆固醇的合成、重吸收和肠道吸收来降低血浆胆固醇水平的重要性。我们还讨论了贝特类药物在调节脂质代谢和改善高密度脂蛋白与低密度脂蛋白比值方面的作用。本研究重点介绍了以前蛋白转化酶枯草溶菌素/克胰蛋白酶 9（PCSK9）单克隆抗体、依维莫司和 microRNA 抑制剂为代表的更近期的分子和遗传干预措施。还特别关注了涉及这些治疗方法的临床试验。
