Rau Oliver, Zettl Heiko, Popescu Laura, Steinhilber Dieter, Schubert-Zsilavecz Manfred
Institute of Pharmaceutcial Chemistry/ZAFES, Johann Wolfgang Goethe University Frankfurt, Max-von-Laue-Strasse 9, 60438 Frankfurt, Germany.
ChemMedChem. 2008 Feb;3(2):206-21. doi: 10.1002/cmdc.200700165.
Dyslipidemia is a pathological alteration of serum lipid levels. The most common forms are either elevations of triglycerides or low density lipoprotein cholesterol associated with a reduction of high density lipoprotein cholesterol. Most frequently both forms of lipid disorders are combined. Elevations of free fatty acid blood levels are commonly not subsumed under the term dyslipidemia. However, free fatty acids should also be considered, as they are frequently associated with dyslipidemia and represent a risk factor for cardiovascular diseases. Dyslipidemias are among the major etiologic factors for arterial occlusive diseases. Resulting in fatal implications such as stroke and coronary heart disease, dyslipidemias contribute to the most prevalent causes of death. Lowering of low density lipoprotein and raising of high density lipoprotein cholesterol levels have been shown in both epidemiologic and intervention studies to decrease mortality. Established treatments of dyslipidemias are statins and fibrates. However, recent research has established some new potential therapeutic targets which are currently investigated in clinical trials. New therapeutic approaches include subtype selective, dual, and pan-agonists of the peroxisome proliferator activated receptor, inhibitors of the cholesterol ester transfer protein, Acyl-CoA-cholesterol-acyltransferase, squalene synthase, microsomal triglycerid-transfer-protein, and cholesterol absorption. Clinical implications of new drugs under investigation are discussed in this review.
血脂异常是血清脂质水平的病理性改变。最常见的形式是甘油三酯升高或低密度脂蛋白胆固醇升高,同时伴有高密度脂蛋白胆固醇降低。两种脂质紊乱形式通常合并存在。游离脂肪酸血水平升高通常不包括在血脂异常这一术语中。然而,游离脂肪酸也应予以考虑,因为它们常与血脂异常相关,并且是心血管疾病的一个危险因素。血脂异常是动脉闭塞性疾病的主要病因之一。血脂异常会导致诸如中风和冠心病等致命后果,是最常见的死亡原因之一。流行病学和干预研究均表明,降低低密度脂蛋白和提高高密度脂蛋白胆固醇水平可降低死亡率。血脂异常的既定治疗方法是他汀类药物和贝特类药物。然而,最近的研究确定了一些新的潜在治疗靶点,目前正在临床试验中进行研究。新治疗方法包括过氧化物酶体增殖物激活受体的亚型选择性、双重和泛激动剂、胆固醇酯转移蛋白抑制剂、酰基辅酶A胆固醇酰基转移酶、角鲨烯合酶、微粒体甘油三酯转移蛋白以及胆固醇吸收抑制剂。本综述讨论了正在研究的新药的临床意义。