他汀类药物通过血管生成调节在心血管疾病中的多效性。

Pleiotropic properties of statins via angiogenesis modulation in cardiovascular disease.

机构信息

Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Research Department, Royal College of Surgeons in Ireland, Bahrain, Adliya, Bahrain.

出版信息

Drug Discov Today. 2022 Oct;27(10):103325. doi: 10.1016/j.drudis.2022.07.010. Epub 2022 Jul 21.

DOI:10.1016/j.drudis.2022.07.010

PMID:35872297

Abstract

Inhibition of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase by statins is affected by inhibiting the active site of the enzyme in a competitive manner. Statins reduce plasma cholesterol by inhibiting its de novo synthesis. In addition, statins impart 'pleiotropic' activities that do not directly relate to their ability to decrease cholesterol. The proangiogenic and antiangiogenic characteristics of statins are among these pleiotropic effects. These angiogenic-modifying properties could offer new therapeutic applications. Statins stimulate or suppress angiogenesis in a biphasic manner. Whereas low doses of statin stimulate angiogenesis, high doses reduce protein prenylation and limit cell development and angiogenesis. In this review, we discuss how statins impact angiogenesis, with a particular focus on angiogenesis in stroke and cardiovascular disease (CVD).

摘要

羟甲基戊二酰辅酶 A（HMG-CoA）还原酶抑制剂通过竞争性抑制酶的活性部位来发挥作用。他汀类药物通过抑制胆固醇的从头合成来降低血浆胆固醇。此外，他汀类药物还具有与其降低胆固醇能力无关的“多效性”作用。他汀类药物的促血管生成和抗血管生成特性就是其中的多效性作用之一。这些血管生成修饰特性可能提供新的治疗应用。他汀类药物以双相方式刺激或抑制血管生成。虽然低剂量的他汀类药物刺激血管生成，但高剂量的他汀类药物会减少蛋白质异戊烯化，限制细胞发育和血管生成。在这篇综述中，我们讨论了他汀类药物如何影响血管生成，特别是在中风和心血管疾病（CVD）中的血管生成。