Scalia Rosario, Stalker Timothy J
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Microcirculation. 2002 Dec;9(6):431-42. doi: 10.1038/sj.mn.7800168.
Statins are inhibitors of the 3-hydroxy-3-methylglutaryl coenzyme A reductase, a ubiquitous enzyme critical for the biosynthesis of cholesterol. Because of their cholesterol-lowering properties, statins are extensively used in medical practice, and large clinical trials have shown that statins effectively reduce cardiovascular related morbidity and mortality. In the past 5 years, an important, new concept suggesting that the cardioprotective effects of statins are not necessarily related to cholesterol-lowering actions has emerged. Indeed, in vivo findings have clearly shown that statins exert anti-inflammatory and immunomodulatory effects and that they modulate vascular remodeling under normocholesterolemic conditions. These pleiotropic properties of statins affect important molecules in vascular biology and help preserve endothelial function in acute and chronic inflammatory states of the cardiovascular system, including coronary and cerebral artery diseases, diabetes, and atherosclerosis. Emerging evidence indicates that the microcirculation is a crucial target for the pleiotropic actions of statins because of its important role in regulating blood flow, leukocyte-endothelium interactions, and vascular remodeling. Accordingly, this review focuses on the role that the microcirculation plays in the vascular protective action of statins.
他汀类药物是3-羟基-3-甲基戊二酰辅酶A还原酶的抑制剂,该酶广泛存在,对胆固醇的生物合成至关重要。由于其降低胆固醇的特性,他汀类药物在医学实践中被广泛使用,大型临床试验表明,他汀类药物能有效降低心血管相关的发病率和死亡率。在过去5年里,一个重要的新概念出现了,即他汀类药物的心脏保护作用不一定与降低胆固醇的作用相关。事实上,体内研究结果清楚地表明,他汀类药物具有抗炎和免疫调节作用,并且在正常胆固醇水平条件下能调节血管重塑。他汀类药物的这些多效性特性影响血管生物学中的重要分子,并有助于在心血管系统的急性和慢性炎症状态(包括冠状动脉疾病、脑动脉疾病、糖尿病和动脉粥样硬化)中维持内皮功能。新出现的证据表明,微循环是他汀类药物多效性作用的关键靶点,因为它在调节血流、白细胞与内皮相互作用以及血管重塑中起重要作用。因此,本综述重点关注微循环在他汀类药物血管保护作用中所起的作用。