Procopio Maria Cristina, Lauro Rita, Nasso Chiara, Carerj Scipione, Squadrito Francesco, Bitto Alessandra, Di Bella Gianluca, Micari Antonio, Irrera Natasha, Costa Francesco
Department of Clinical and Experimental Medicine, University of Messina, 98165 Messina, Italy.
Department of Biomedical and Dental Sciences and Morphological and Functional Imaging, University of Messina, A.O.U. Policlinic "G. Martino", 98165 Messina, Italy.
Biomedicines. 2021 Feb 18;9(2):204. doi: 10.3390/biomedicines9020204.
Myocardial infarction (MI) is a dramatic event often caused by atherosclerotic plaque erosion or rupture and subsequent thrombotic occlusion of a coronary vessel. The low supply of oxygen and nutrients in the infarcted area may result in cardiomyocytes necrosis, replacement of intact myocardium with non-contractile fibrous tissue and left ventricular (LV) function impairment if blood flow is not quickly restored. In this review, we summarized the possible correlation between adenosine system, purinergic system and Wnt/β-catenin pathway and their role in the pathogenesis of cardiac damage following MI. In this context, several pathways are involved and, in particular, the adenosine receptors system shows different interactions between its members and purinergic receptors: their modulation might be effective not only for a normal functional recovery but also for the treatment of heart diseases, thus avoiding fibrosis, reducing infarcted area and limiting scaring. Similarly, it has been shown that Wnt/β catenin pathway is activated following myocardial injury and its unbalanced activation might promote cardiac fibrosis and, consequently, LV systolic function impairment. In this regard, the therapeutic benefits of Wnt inhibitors use were highlighted, thus demonstrating that Wnt/β-catenin pathway might be considered as a therapeutic target to prevent adverse LV remodeling and heart failure following MI.
心肌梗死(MI)是一种常由动脉粥样硬化斑块侵蚀或破裂以及随后冠状动脉血栓性闭塞引起的严重事件。如果血流不能迅速恢复,梗死区域氧气和营养物质供应不足可能导致心肌细胞坏死,完整心肌被无收缩功能的纤维组织替代以及左心室(LV)功能受损。在本综述中,我们总结了腺苷系统、嘌呤能系统与Wnt/β-连环蛋白信号通路之间可能的关联及其在心肌梗死后心脏损伤发病机制中的作用。在此背景下,涉及多种信号通路,特别是腺苷受体系统的成员之间以及与嘌呤能受体之间存在不同的相互作用:对它们的调节不仅可能对正常功能恢复有效,而且对心脏病治疗也有效,从而避免纤维化、缩小梗死面积并限制瘢痕形成。同样,研究表明心肌损伤后Wnt/β-连环蛋白信号通路被激活,其失衡激活可能促进心脏纤维化,进而导致左心室收缩功能受损。在这方面,使用Wnt抑制剂的治疗益处得到了强调,从而表明Wnt/β-连环蛋白信号通路可被视为预防心肌梗死后不良左心室重构和心力衰竭的治疗靶点。