Histones and heart failure in diabetes

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.