Chowdhury Kaushik, Lai Shih-Lei, Marín-Juez Rubén
Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
Taiwan International Graduate Program in Molecular Medicine, National Yang Ming Chiao Tung University and Academia Sinica, Taipei, Taiwan.
Methods Mol Biol. 2022;2475:297-312. doi: 10.1007/978-1-0716-2217-9_22.
Over the last decades, myocardial infarction and heart failure have accounted every year for millions of deaths worldwide. After a coronary occlusion, the lack of blood supply to downstream muscle leads to cell death and scarring. To date, several pro-angiogenic factors have been tested to stimulate reperfusion of the affected myocardium, VEGFA being one of the most extensively studied. Given the unsuccessful outcomes of clinical trials, understanding how cardiac revascularization takes place in models with endogenous regenerative capacity holds the key to devising more efficient therapies. Here, we summarize the main findings on VEGFA's role during cardiac repair and regeneration, with a particular focus on zebrafish as a regenerative model. Moreover, we provide a comprehensive overview of available tools to modulate Vegfa expression and action in zebrafish regeneration studies. Understanding the role of Vegfa during zebrafish heart regeneration may help devise efficient therapies and circumvent current limitations in using VEGFA for therapeutic angiogenesis approaches.
在过去几十年里,心肌梗死和心力衰竭每年在全球导致数百万人死亡。冠状动脉闭塞后,下游心肌供血不足会导致细胞死亡和瘢痕形成。迄今为止,已经测试了几种促血管生成因子以刺激受影响心肌的再灌注,血管内皮生长因子A(VEGFA)是研究最广泛的因子之一。鉴于临床试验的不成功结果,了解具有内源性再生能力的模型中心脏血管再生的发生方式是设计更有效疗法的关键。在这里,我们总结了VEGFA在心脏修复和再生过程中作用的主要发现,特别关注斑马鱼作为再生模型。此外,我们全面概述了在斑马鱼再生研究中调节Vegfa表达和作用的可用工具。了解Vegfa在斑马鱼心脏再生过程中的作用可能有助于设计有效的疗法,并规避目前在使用VEGFA进行治疗性血管生成方法时的局限性。