Ferenczyová Kristína, Kindernay Lucia, Vlkovičová Jana, Kaločayová Barbora, Rajtík Tomáš, Barteková Monika
Centre of Experimental Medicine, Institute for Heart Research, Slovak Academy of Sciences, Dúbravská cesta 9, 84104 Bratislava, Slovakia.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University in Bratislava, Odbojárov 10, 83232 Bratislava, Slovakia.
Antioxidants (Basel). 2021 Aug 30;10(9):1390. doi: 10.3390/antiox10091390.
Catechins represent a group of polyphenols that possesses various beneficial effects in the cardiovascular system, including protective effects in cardiac ischemia-reperfusion (I/R) injury, a major pathophysiology associated with ischemic heart disease, myocardial infarction, as well as with cardioplegic arrest during heart surgery. In particular, catechin, (-)-epicatechin, and epigallocatechin gallate (EGCG) have been reported to prevent cardiac myocytes from I/R-induced cell damage and I/R-associated molecular changes, finally, resulting in improved cell viability, reduced infarct size, and improved recovery of cardiac function after ischemic insult, which has been widely documented in experimental animal studies and cardiac-derived cell lines. Cardioprotective effects of catechins in I/R injury were mediated via multiple molecular mechanisms, including inhibition of apoptosis; activation of cardioprotective pathways, such as PI3K/Akt (RISK) pathway; and inhibition of stress-associated pathways, including JNK/p38-MAPK; preserving mitochondrial function; and/or modulating autophagy. Moreover, regulatory roles of several microRNAs, including miR-145, miR-384-5p, miR-30a, miR-92a, as well as lncRNA MIAT, were documented in effects of catechins in cardiac I/R. On the other hand, the majority of results come from cell-based experiments and healthy small animals, while studies in large animals and studies including comorbidities or co-medications are rare. Human studies are lacking completely. The dosages of compounds also vary in a broad scale, thus, pharmacological aspects of catechins usage in cardiac I/R are inconclusive so far. Therefore, the aim of this focused review is to summarize the most recent knowledge on the effects of catechins in cardiac I/R injury and bring deep insight into the molecular mechanisms involved and dosage-dependency of these effects, as well as to outline potential gaps for translation of catechin-based treatments into clinical practice.
儿茶素是一类多酚,在心血管系统中具有多种有益作用,包括对心脏缺血再灌注(I/R)损伤的保护作用。心脏缺血再灌注损伤是与缺血性心脏病、心肌梗死以及心脏手术期间心脏停搏相关的主要病理生理学过程。特别是,据报道儿茶素、(-)-表儿茶素和表没食子儿茶素没食子酸酯(EGCG)可防止心肌细胞受到I/R诱导的细胞损伤和I/R相关的分子变化,最终提高细胞活力、减小梗死面积并改善缺血性损伤后心脏功能的恢复,这在实验动物研究和心脏来源的细胞系中已有广泛记载。儿茶素对I/R损伤的心脏保护作用是通过多种分子机制介导的,包括抑制细胞凋亡;激活心脏保护途径,如PI3K/Akt(RISK)途径;抑制应激相关途径,包括JNK/p38-MAPK;维持线粒体功能;和/或调节自噬。此外,还记录了几种微小RNA(包括miR-145、miR-384-5p、miR-30a、miR-92a)以及长链非编码RNA MIAT在儿茶素对心脏I/R作用中的调节作用。另一方面,大多数结果来自基于细胞的实验和健康的小动物,而对大型动物的研究以及包括合并症或联合用药的研究很少。完全缺乏人体研究。化合物的剂量范围也差异很大。因此,到目前为止,儿茶素在心脏I/R中使用的药理学方面尚无定论。因此,本聚焦综述的目的是总结儿茶素对心脏I/R损伤作用的最新知识,深入了解其涉及的分子机制和这些作用的剂量依赖性,并概述将基于儿茶素的治疗转化为临床实践的潜在差距。