Laboratory of Biochemistry, Faculty of Chemistry, National and Kapodistrian University, Athens, Greece.
Angiology. 2011 Apr;62(3):209-18. doi: 10.1177/0003319710375089. Epub 2010 Aug 29.
Platelet activating factor (PAF) is implicated in cardiovascular disease (CVD). Statins are widely used in these situations. Therefore, we assessed their effect on the biological activities and metabolism of PAF. Several statins, including simvastatin, exhibited an inhibitory effect against PAF, comparable with that of PAF-inhibitors. Simvastatin also suppressed in vivo PAF-biosynthesis via the de novo pathway, in leukocytes of 6 simvastatin-treated volunteers. Total cholesterol and low-density lipoprotein cholesterol were also significantly decreased, whereas high-density lipoprotein cholesterol, triacylglycerol, EC(50), and lag time were unaffected in these participants. Simvastatin with an intact lactone ring also inhibited PAF-activities, while incubation of human mesangial cells with it also resulted in decreased de novo PAF-biosynthesis. This suggests that these simvastatin-dependent effects are independent of its lactone ring. These new actions of statins should be further studied in PAF-implicated pathological conditions such as CVD, cancer, and renal disease.
血小板激活因子（PAF）与心血管疾病（CVD）有关。他汀类药物在这些情况下被广泛应用。因此，我们评估了它们对 PAF 生物活性和代谢的影响。几种他汀类药物，包括辛伐他汀，对 PAF 表现出抑制作用，与 PAF 抑制剂相当。辛伐他汀还通过从头途径抑制白细胞中 PAF 的生物合成，在 6 名辛伐他汀治疗志愿者的白细胞中。总胆固醇和低密度脂蛋白胆固醇也显著降低，而高密度脂蛋白胆固醇、三酰甘油、EC（50）和滞后时间在这些参与者中不受影响。具有完整内酯环的辛伐他汀也抑制了 PAF 活性，而与人系膜细胞孵育也导致从头合成 PAF 的减少。这表明这些辛伐他汀依赖性作用与其内酯环无关。这些他汀类药物的新作用应在涉及 PAF 的病理条件（如 CVD、癌症和肾脏疾病）中进一步研究。
