Department of Clinical and Biological Sciences, University of Turin, Regione Gonzole 10, 10043 Orbassano, Italy.
Int J Mol Sci. 2024 Nov 1;25(21):11747. doi: 10.3390/ijms252111747.
Myocardial infarction (MI) is a critical global health issue and a leading cause of heart failure. Indeed, while neonatal mammals can regenerate cardiac tissue mainly through cardiomyocyte proliferation, this ability is lost shortly after birth, resulting in the adult heart's inability to regenerate after injury effectively. In adult mammals, the adverse cardiac remodelling, which compensates for the loss of cardiac cells, impairs cardiac function due to the non-contractile nature of fibrotic tissue. Moreover, the neovascularisation after MI is inadequate to restore blood flow to the infarcted myocardium. This review aims to synthesise the most recent insights into the molecular and cellular players involved in endogenous myocardial and vascular regeneration, facilitating the identification of mechanisms that could be targeted to trigger cardiac regeneration, reduce fibrosis, and improve functional recovery post-MI. Reprogramming adult cardiomyocytes to regain their proliferative potential, along with the modulation of target cells responsible for neovascularisation, represents promising therapeutic strategies. An updated overview of endogenous mechanisms that regulate both myocardial and coronary vasculature regeneration-including stem and progenitor cells, growth factors, cell cycle regulators, and key signalling pathways-could help identify new critical intervention points for therapeutic applications.
心肌梗死（MI）是一个全球性的重大健康问题，也是心力衰竭的主要原因。事实上，虽然新生哺乳动物主要通过心肌细胞增殖来再生心脏组织，但这种能力在出生后不久就会丧失，导致成年心脏在受伤后无法有效再生。在成年哺乳动物中，由于纤维组织的非收缩性，代偿性心肌细胞损失的不良心脏重构会损害心脏功能。此外，MI 后的新血管生成不足以恢复梗死心肌的血流。本综述旨在综合最新的关于内源性心肌和血管再生所涉及的分子和细胞成分的见解，有助于确定可以靶向的机制，以触发心脏再生、减少纤维化并改善 MI 后的功能恢复。重编程成年心肌细胞以恢复其增殖潜能，以及调节负责新血管生成的靶细胞，代表了很有前途的治疗策略。对调节心肌和冠状动脉血管再生的内源性机制的最新综述，包括干细胞和祖细胞、生长因子、细胞周期调节剂和关键信号通路，可以帮助确定治疗应用的新的关键干预点。
