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用于治疗心血管疾病的热量限制模拟物。

Caloric restriction mimetics for the treatment of cardiovascular diseases.

作者信息

Sciarretta Sebastiano, Forte Maurizio, Castoldi Francesca, Frati Giacomo, Versaci Francesco, Sadoshima Junichi, Kroemer Guido, Maiuri Maria Chiara

机构信息

Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Corso della Repubblica 79, 40100 Latina, Italy.

Department of AngioCardioNeurology, IRCCS Neuromed, Pozzilli (IS), Italy.

出版信息

Cardiovasc Res. 2021 May 25;117(6):1434-1449. doi: 10.1093/cvr/cvaa297.

Abstract

Caloric restriction mimetics (CRMs) are emerging as potential therapeutic agents for the treatment of cardiovascular diseases. CRMs include natural and synthetic compounds able to inhibit protein acetyltransferases, to interfere with acetyl coenzyme A biosynthesis, or to activate (de)acetyltransferase proteins. These modifications mimic the effects of caloric restriction, which is associated with the activation of autophagy. Previous evidence demonstrated the ability of CRMs to ameliorate cardiac function and reduce cardiac hypertrophy and maladaptive remodelling in animal models of ageing, mechanical overload, chronic myocardial ischaemia, and in genetic and metabolic cardiomyopathies. In addition, CRMs were found to reduce acute ischaemia-reperfusion injury. In many cases, these beneficial effects of CRMs appeared to be mediated by autophagy activation. In the present review, we discuss the relevant literature about the role of different CRMs in animal models of cardiac diseases, emphasizing the molecular mechanisms underlying the beneficial effects of these compounds and their potential future clinical application.

摘要

热量限制模拟物(CRMs)正逐渐成为治疗心血管疾病的潜在治疗药物。CRMs包括能够抑制蛋白质乙酰转移酶、干扰乙酰辅酶A生物合成或激活(去)乙酰转移酶蛋白的天然和合成化合物。这些修饰模拟了热量限制的效果,而热量限制与自噬的激活有关。先前的证据表明,在衰老、机械过载、慢性心肌缺血的动物模型以及遗传和代谢性心肌病中,CRMs具有改善心脏功能、减轻心脏肥大和适应性不良重塑的能力。此外,还发现CRMs可减轻急性缺血-再灌注损伤。在许多情况下,CRMs的这些有益作用似乎是由自噬激活介导的。在本综述中,我们讨论了关于不同CRMs在心脏病动物模型中作用的相关文献,强调了这些化合物有益作用的分子机制及其潜在的未来临床应用。

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