Bedi Onkar, Dhawan Veena, Sharma P L, Kumar Puneet
Department of Experimental Medicine and Biotechnology, Post Graduate Institute of Medical Education & Research (PGIMER), Chandigarh, India.
Department of Pharmacology, Post Graduate Institute of Medical Education & Research (PGIMER), Chandigarh, India.
Naunyn Schmiedebergs Arch Pharmacol. 2016 Jul;389(7):695-712. doi: 10.1007/s00210-016-1252-4. Epub 2016 May 5.
The HMG Co-enzyme inhibitors and new lipid-modifying agents expand their new therapeutic target options in the field of medical profession. Statins have been described as the most effective class of drugs to reduce serum cholesterol levels. Since the discovery of the first statin nearly 30 years ago, these drugs have become the main therapeutic approach to lower cholesterol levels. The present scientific research demonstrates numerous non-lipid modifiable effects of statins termed as pleiotropic effects of statins, which could be beneficial for the treatment of various devastating disorders. The most important positive effects of statins are anti-inflammatory, anti-proliferative, antioxidant, immunomodulatory, neuroprotective, anti-diabetes, and antithrombotic, improving endothelial dysfunction and attenuating vascular remodeling besides many others which are discussed under the scope of this review. In particular, inhibition of Rho and its downstream target, Rho-associated coiled-coil-containing protein kinase (ROCK), and their agonistic action on peroxisome proliferator-activated receptors (PPARs) can be viewed as the principle mechanisms underlying the pleiotropic effects of statins. With gradually increasing knowledge of new therapeutic targets of statins, their use has also been advocated in chronic inflammatory disorders for example rheumatoid arthritis (RA) and in systemic lupus erythematosus (SLE). In the scope of review, we highlight statins and their pleiotropic effects with reference to their harmful and beneficial effects as a novel approach for their use in the treatment of devastating disorders. Graphical abstract Pleiotropic effect of statins.
HMG辅酶抑制剂和新型脂质调节药物在医学领域拓展了新的治疗靶点选择。他汀类药物被认为是降低血清胆固醇水平最有效的一类药物。自近30年前发现第一种他汀类药物以来，这些药物已成为降低胆固醇水平的主要治疗方法。目前的科学研究表明，他汀类药物具有许多非脂质调节作用，即他汀类药物的多效性作用，这可能对治疗各种严重疾病有益。他汀类药物最重要的积极作用包括抗炎、抗增殖、抗氧化、免疫调节、神经保护、抗糖尿病和抗血栓形成，除了许多其他作用外，还能改善内皮功能障碍和减轻血管重塑，这些将在本综述范围内进行讨论。特别是，抑制Rho及其下游靶点含Rho相关卷曲螺旋的蛋白激酶（ROCK），以及它们对过氧化物酶体增殖物激活受体（PPARs）的激动作用，可被视为他汀类药物多效性作用的主要机制。随着对他汀类药物新治疗靶点的认识逐渐增加，它们也被提倡用于慢性炎症性疾病，例如类风湿性关节炎（RA）和系统性红斑狼疮（SLE）。在本综述范围内，我们将强调他汀类药物及其多效性作用，同时提及它们的有害和有益作用，作为其用于治疗严重疾病的一种新方法。图形摘要 他汀类药物的多效性作用
