Department of Physiology, Anatomy and Genetics, University of Oxford, UK.
Vascul Pharmacol. 2013 Mar;58(3):164-73. doi: 10.1016/j.vph.2012.08.001. Epub 2012 Aug 11.
While cardiovascular diseases remain the major worldwide cause of mortality and morbidity, there is an urgent need to tackle the clinical and economic burden of heart failure. Since the mammalian heart is unable to adequately regenerate beyond early postnatal stages, individuals surviving acute myocardial infarction are at risk of heart failure. Understanding the embryonic mechanisms of vasculogenesis and cardiogenesis, as well as the mechanisms retained for regeneration in species such as the zebrafish, will inform on strategies for human myocardial repair. Due to their fundamental role in heart development, epicardium-derived cells (EPDCs) have emerged as a population with potential to restore myocardium and coronary vasculature. The ability to revive ordinarily dormant EPDCs lies in the identification of key molecular cues used in the embryo to orchestrate cardiovascular development. One such stimulatory factor, Thymosin β4 (Tβ4), restores the quiescent adult epicardium to its pluripotent embryonic state. Tβ4 treatment of infarcted hearts induces dramatic EPDC proliferation and formation of a network of perfused, functional vessels to enhance blood flow to the ischaemic myocardium. Moreover, Tβ4 facilitates an epicardial contribution of mature de novo cardiomyocytes, structurally and functionally coupled with resident myocardium, which may contribute towards the functional improvement of Tβ4-treated hearts post-MI.
虽然心血管疾病仍然是全球主要的死亡和发病原因，但迫切需要解决心力衰竭的临床和经济负担。由于哺乳动物的心脏在出生后早期阶段之后无法充分再生，因此急性心肌梗死的幸存者有患心力衰竭的风险。了解血管生成和心肌发生的胚胎机制，以及斑马鱼等物种中保留的再生机制，将为人类心肌修复提供信息。由于其在心脏发育中的基本作用，心外膜衍生细胞（EPDC）已成为具有恢复心肌和冠状动脉血管潜力的群体。恢复通常处于休眠状态的 EPDC 的能力在于确定胚胎中用于协调心血管发育的关键分子线索。一种这样的刺激因子，胸腺素 β4（Tβ4），将静止的成年心外膜恢复到其多能胚胎状态。Tβ4 处理梗死心脏可诱导 EPDC 的剧烈增殖并形成灌注的功能血管网络，从而增强血流到缺血心肌。此外，Tβ4 促进成熟的新生成的心肌细胞在心外膜中的贡献，与驻留的心肌结构和功能相连，这可能有助于 Tβ4 处理后的心脏在心肌梗死后的功能改善。
