The Third Department of Cardiology, Jiangxi Provincial People's Hospital, Nanchang, China.
Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
Cardiovasc Ther. 2018 Aug;36(4):e12331. doi: 10.1111/1755-5922.12331. Epub 2018 May 4.
Heat shock proteins (HSPs) are an important family of protective proteins. They are involved actively in an array of cellular processes, including protective effects on the cardiovascular system in response to various stimuli. Increasing evidence shows that pharmacologic interventions that induce expression of HSPs may be a novel approach for the treatment of cardiovascular diseases. However, agents that induce expression of HSPs used previously are toxic or have harmful side effects, which limit their clinical application. Geranylgeranylacetone (GGA) is not only a widely used antiulcer agent in Asia, but also a nontoxic inducer of HSPs expression. It increases the expression of HSPs rapidly in the presence of ischemia, anoxia, oxidative stress, and toxicants, thereby having significant protective effects. The cardioprotective effects of GGA have been corroborated by experiments in vivo and in vitro. Importantly, several derivatives of GGA have been synthesized that have improved pharmaco-chemical and HSPs-boosting properties. In this review, the current knowledge and potential cardioprotective mechanisms of GGA are summarized comprehensively. We discuss the protective effects of GGA in cardiovascular diseases and myocardial injury induced by physical or chemical injury. Currently available information suggests that GGA could be employed as a novel pharmacologic intervention against cardiovascular disease.
热休克蛋白(HSPs)是一类重要的保护蛋白。它们积极参与多种细胞过程,包括对心血管系统的保护作用,以应对各种刺激。越来越多的证据表明,诱导 HSPs 表达的药物干预可能是治疗心血管疾病的一种新方法。然而,以前使用的诱导 HSPs 表达的药物具有毒性或有害的副作用,限制了它们的临床应用。金合欢素(GGA)不仅是亚洲广泛使用的抗溃疡剂,也是 HSPs 表达的无毒诱导剂。它在缺血、缺氧、氧化应激和毒物存在的情况下迅速增加 HSPs 的表达,从而具有显著的保护作用。GGA 的心脏保护作用已在体内和体外实验中得到证实。重要的是,已经合成了几种 GGA 的衍生物,它们具有改善的药化和 HSPs 促进特性。在这篇综述中,全面总结了 GGA 的现有知识和潜在的心脏保护机制。我们讨论了 GGA 在心血管疾病和物理或化学损伤引起的心肌损伤中的保护作用。目前的信息表明,GGA 可以作为一种新的药物干预手段,用于治疗心血管疾病。