Yerra Veera Ganesh, Advani Andrew
Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael's Hospital, 6-151, 61 Queen Street East, Toronto, ON, M5C 2T2, Canada.
Cell Mol Life Sci. 2018 Sep;75(17):3193-3213. doi: 10.1007/s00018-018-2857-1. Epub 2018 Jun 22.
Although heart failure is now accepted as being a major long-term complication of diabetes, many of the recent advances in our understanding of the pathobiology of diabetes complications have come about through the study of more traditional microvascular or macrovascular diseases. This has been the case, for example, in the evolving field of the epigenetics of diabetes complications and, in particular, the post-translational modification of histone proteins. However, histone modifications also occur in human heart failure and their perturbation also occurs in diabetic hearts. Here, we review the principal histone modifications and their enzymatic writers and erasers that have been studied to date; we discuss what is currently known about their roles in heart failure and in the diabetic heart; we draw on lessons learned from the studies of microvascular and macrovascular complications; and we speculate that therapeutically manipulating histone modifications may alter the natural history of heart failure in diabetes.
尽管心力衰竭目前已被公认为糖尿病的一种主要长期并发症，但我们对糖尿病并发症病理生物学的许多最新认识进展是通过对更传统的微血管或大血管疾病的研究取得的。例如，在糖尿病并发症表观遗传学这一不断发展的领域，尤其是组蛋白的翻译后修饰方面，情况就是如此。然而，组蛋白修饰也发生在人类心力衰竭中，并且在糖尿病心脏中也会出现其紊乱。在此，我们综述了迄今为止已研究的主要组蛋白修饰及其酶促写入和擦除因子；我们讨论了目前已知它们在心力衰竭和糖尿病心脏中的作用；我们借鉴了微血管和大血管并发症研究中的经验教训；并且我们推测通过治疗手段操纵组蛋白修饰可能会改变糖尿病心力衰竭的自然病程。
