British Heart Foundation Centre of Regenerative Medicine, Burdon Sanderson Cardiac Science Centre, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
Ludwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Nat Rev Cardiol. 2020 Dec;17(12):790-806. doi: 10.1038/s41569-020-0400-1. Epub 2020 Jun 25.
The formation of new blood vessels after myocardial infarction (MI) is essential for the survival of existing and regenerated cardiac tissue. However, the extent of endogenous revascularization after MI is insufficient, and MI can often result in ventricular remodelling, progression to heart failure and premature death. The neutral results of numerous clinical trials that have evaluated the efficacy of angiogenic therapy to revascularize the infarcted heart reflect our poor understanding of the processes required to form a functional coronary vasculature. In this Review, we describe the latest advances in our understanding of the processes involved in coronary vessel formation, with mechanistic insights taken from developmental studies. Coronary vessels originate from multiple cellular sources during development and form through a number of distinct and carefully orchestrated processes. The ectopic reactivation of developmental programmes has been proposed as a new paradigm for regenerative medicine, therefore, a complete understanding of these processes is crucial. Furthermore, knowledge of how these processes differ between the embryonic and adult heart, and how they might be more closely recapitulated after injury are critical for our understanding of regenerative biology, and might facilitate the identification of tractable molecular targets to therapeutically promote neovascularization and regeneration of the infarcted heart.
心肌梗死后（MI）新血管的形成对于现有和再生的心肌组织的存活至关重要。然而，MI 后的内源性再血管化程度不足，并且 MI 通常会导致心室重构、进展为心力衰竭和过早死亡。众多评估血管生成治疗以使梗死心脏再血管化的疗效的临床试验的中性结果反映了我们对形成功能性冠状动脉血管所需过程的理解不足。在这篇综述中，我们描述了对涉及冠状动脉血管形成过程的最新理解，这些理解来自发育研究中的机制见解。在发育过程中，冠状动脉起源于多个细胞来源，并通过多个独特且精心协调的过程形成。发育程序的异位重新激活被提议作为再生医学的新范例，因此，对这些过程的完整理解至关重要。此外，了解这些过程在胚胎和成年心脏之间的差异，以及它们在受伤后如何更紧密地再现，对于我们理解再生生物学至关重要，并可能有助于确定可行的分子靶点，以治疗性促进梗死心脏的新生血管形成和再生。
