Hoeg J M, Brewer H B
Molecular Disease Branch, National Heart, Lung, and Blood Institute, Bethesda, Md 20892.
JAMA. 1987 Dec 25;258(24):3532-6.
A new class of drugs, which inhibit de novo cholesterol biosynthesis, significantly reduces the blood cholesterol concentrations in hypercholesterolemic patients. Four separate inhibitors have lowered plasma total cholesterol and low-density lipoprotein (LDL) levels in humans by 20% to 40%: mevastatin (Compactin), lovastatin (mevinolin), pravastatin (CS-514, Eptastatin, and SQ 31000), and simvastatin (Synvinolin, MK-733). In addition to lowering total and LDL cholesterol concentrations, the plasma concentration of the potentially atherogenic B apolipoprotein is also reduced by 20% to 40%. The reduction in the levels of circulating atherogenic lipoprotein particles occurs as a result of decreased synthesis and enhanced removal of LDLs by the LDL receptor pathway in hepatocytes. Moreover, the levels of high-density lipoprotein cholesterol, which are inversely related to atherosclerosis, increase in concentration with treatment by these drugs. If the short-term safety of these drugs extends to ongoing long-term studies and if cardiovascular morbidity and mortality are affected by their use, this class of hypolipidemic agent will markedly facilitate the effective treatment of hypercholesterolemia.
一类新的抑制胆固醇从头生物合成的药物，能显著降低高胆固醇血症患者的血液胆固醇浓度。四种不同的抑制剂已使人体血浆总胆固醇和低密度脂蛋白（LDL）水平降低了20%至40%：美伐他汀（康帕丁）、洛伐他汀（美维诺林）、普伐他汀（CS - 514、依普他他汀和SQ 31000）以及辛伐他汀（舒降之、MK - 733）。除了降低总胆固醇和LDL胆固醇浓度外，具有潜在致动脉粥样硬化作用的B载脂蛋白的血浆浓度也降低了20%至40%。循环中致动脉粥样硬化脂蛋白颗粒水平的降低是由于肝细胞中LDL受体途径对LDL的合成减少和清除增强所致。此外，与动脉粥样硬化呈负相关的高密度脂蛋白胆固醇水平在使用这些药物治疗后浓度会升高。如果这些药物的短期安全性能延续到正在进行的长期研究中，并且如果它们的使用会影响心血管疾病的发病率和死亡率，那么这类降血脂药物将显著促进高胆固醇血症的有效治疗。
