Johnston T P, Korolenko T A, Pirro M, Sahebkar A
Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO 64108-2718, USA.
Institute of Physiology and Fundamental Medicine, Timakov St. 4, Novosibirsk, 630117, Russia.
Pharmacol Res. 2017 Jun;120:219-225. doi: 10.1016/j.phrs.2017.04.008. Epub 2017 Apr 10.
Hypercholesterolemia is one of the major risk factors for the development of cardiovascular disease. Atherosclerosis resulting from hypercholesterolemia causes many serious cardiovascular diseases. Statins are generally accepted as a treatment of choice for lowering low-density lipoprotein (LDL) cholesterol, which reduces coronary heart disease morbidity and mortality. Since statin use can be associated with muscle problems and other adverse symptoms, non-adherence and discontinuation of statin therapy often leads to inadequate control of plasma cholesterol levels and increased cardiovascular risk. Moreover, there is compelling evidence on the presence of still considerable residual cardiovascular risk in statin-treated patients. Ezetimibe improves cholesterol-lowering efficacy and provides mild additional cardiovascular protection when combined with statin treatment. Despite a favorable safety profile compared to statins, ezetimibe-induced cholesterol-lowering is modest when used alone. Hence, there is a critical need to identity additional effective hypolipidemic agents that can be used either in combination with statins, or alone, if statins are not tolerated. Thus, hypolipidemic agents such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, apolipoprotein B-100 antisense oligonucleotides, cholesteryl ester transfer protein (CETP) inhibitors, and microsomal triglyceride transfer protein (MTTP) inhibitors, as well as yeast polysaccharides (beta-glucans and mannans) and compounds derived from natural sources (nutraceuticals) such as glucomannans, plant sterols, berberine, and red yeast rice are being used. In this review, we will discuss hypercholesterolemia, its impact on the development of cardiovascular disease (CVD), and the use of yeast polysaccharides, various nutraceuticals, and several therapeutic agents not derived from 'natural' sources, to treat hypercholesterolemia.
高胆固醇血症是心血管疾病发生的主要危险因素之一。高胆固醇血症导致的动脉粥样硬化会引发许多严重的心血管疾病。他汀类药物通常被认为是降低低密度脂蛋白（LDL）胆固醇的首选治疗药物，可降低冠心病的发病率和死亡率。由于使用他汀类药物可能会出现肌肉问题和其他不良症状，不坚持使用或停用他汀类药物治疗往往会导致血浆胆固醇水平控制不佳，增加心血管疾病风险。此外，有确凿证据表明，接受他汀类药物治疗的患者仍存在相当大的心血管残留风险。依折麦布可提高降胆固醇疗效，与他汀类药物联合使用时可提供轻度的额外心血管保护作用。尽管与他汀类药物相比，依折麦布的安全性较好，但单独使用时其降胆固醇作用较为有限。因此，迫切需要确定其他有效的降血脂药物，这些药物既可以与他汀类药物联合使用，也可以在患者不耐受他汀类药物时单独使用。因此，目前正在使用的降血脂药物包括前蛋白转化酶枯草溶菌素/kexin 9型（PCSK9）抑制剂、载脂蛋白B-100反义寡核苷酸、胆固醇酯转运蛋白（CETP）抑制剂、微粒体甘油三酯转运蛋白（MTTP）抑制剂，以及酵母多糖（β-葡聚糖和甘露聚糖）和来自天然来源的化合物（营养保健品），如葡甘露聚糖、植物甾醇、黄连素和红曲米。在本综述中，我们将讨论高胆固醇血症、其对心血管疾病（CVD）发生的影响，以及酵母多糖、各种营养保健品和几种非“天然”来源的治疗药物在治疗高胆固醇血症方面的应用。
