Yester Jessie Wettig, Kühn Bernhard
Children's Hospital of Pittsburgh of UPMC, Department of Pediatrics, University of Pittsburgh School of Medicine, 4401 Penn Ave, Pittsburgh, PA, 15224-1334, USA.
Richard King Mellon Foundation Institute for Pediatric Research and Division of Cardiology, Children's Hospital of Pittsburgh of UPMC, and Department of Pediatrics, University of Pittsburgh School of Medicine, 4401 Penn Ave, Pittsburgh, PA, 15224-1334, USA.
Curr Cardiol Rep. 2017 Feb;19(2):13. doi: 10.1007/s11886-017-0826-1.
Congenital heart disease is the most common birth defect and acquired heart disease is the leading cause of death in adults. Understanding the mechanisms that drive cardiomyocyte proliferation and differentiation has the potential to advance the understanding and potentially the treatment of different cardiac pathologies, ranging from myopathies and heart failure to myocardial infarction. This review focuses on studies aimed at elucidating signal transduction pathways and molecular mechanisms that promote proliferation, differentiation, and regeneration of differentiated heart muscle cells, cardiomyocytes.
There is now significant evidence that demonstrates cardiomyocytes continue to proliferate into adulthood. Potential regulators have been identified, including cell cycle regulators, extracellular ligands such as neuregulin, epigenetic targets, reactive oxygen species, and microRNA. The necessary steps should involve validating and applying the new knowledge about cardiomyocyte regeneration towards the development of therapeutic targets for patients. This will be facilitated by the application of standardized pre-clinical models to study cardiomyocyte regeneration.
先天性心脏病是最常见的出生缺陷,而获得性心脏病是成年人的主要死因。了解驱动心肌细胞增殖和分化的机制,有可能增进对各种心脏疾病的理解,并可能推动其治疗,这些疾病包括心肌病、心力衰竭和心肌梗死等。本综述聚焦于旨在阐明促进分化的心肌细胞(即心肌细胞)增殖、分化和再生的信号转导途径及分子机制的研究。
目前有大量证据表明心肌细胞在成年后仍会继续增殖。已确定了潜在的调节因子,包括细胞周期调节因子、细胞外配体(如神经调节蛋白)、表观遗传靶点、活性氧和微小RNA。必要的步骤应包括验证并应用有关心肌细胞再生的新知识,以开发针对患者的治疗靶点。应用标准化的临床前模型来研究心肌细胞再生将有助于实现这一点。