高密度脂蛋白靶向防治动脉粥样硬化新进展

New progress of high density lipoprotein targeting prevention and therapy for atherosclerosis

许多随机临床试验已经明确,他汀类药物因为可以降低低密度脂蛋白胆固醇水平并轻度增加高密度脂蛋白胆固醇(HDLC)水平,已经成为防治动脉粥样硬化(As)疾病的主要标准疗法。高密度脂蛋白(HDL)颗粒介导的胆固醇逆转运(RCT)途径具有抗As的作用。目前HDL靶向治疗的重要途径已经不是升高HDLC水平,更多的是通过改善HDL功能,增强血浆胆固醇的清除,以及预防和减轻与As有关的炎症。胆固醇酯转移蛋白抑制剂可增加正常或低HDLC患者的HDLC水平;肝X受体激动剂可通过增加RCT减少As;使用重组HDL的HDL治疗在动物模型中显著有效;在细胞以及动物模型中研究发现,通过干预某些基因靶点,可使HDLC的水平和HDL功能得到改善。回顾相关文献,我们认为:HDL靶向治疗有防治As的潜力,可能对心血管疾病患者有效。

Numerous randomized clinical trials have established statins as the major standard therapy for atherosclerotic diseases because these molecules decrease the plasma level of low density lipoprotein cholesterol and moderately increase the plasma level of high density lipoprotein cholesterol( HDLC). The reverse cholesterol transport( RCT) pathway,mediated by HDL particles,has a relevant antiatherogenic potential. An important approach to HDL-targeted therapy is not optimization of the HDLC level but by improving HDL function,enhancing plasma cholesterol clearance,and preventing and reducing atherosclerosis related inflammation. Small-molecule inhibitors of cholesteryl ester transfer protein increase the HDLC level in subjects with normal or low HDLC. LXR agonists can reduce As by increasing RCT. HDL therapies using reconstituted HDL are dramatically effective in animal models. And,in cell and animal models,studies have found that by interfering with certain gene targets,the cholesterol level and function of HDL can be improved. Our review of the literature leads us to conclude that HDL-targeted therapies have significant atheroprotective potential and thus may effectively treat patients with cardiovascular diseases.