Dr Carolyn Lam:                Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the Journal and its editors. I'm Dr Carolyn Lam, associate editor from the National Heart Center in Duke National University of Singapore. Dr Greg Hundley:             And I'm Greg Hundley, also associate editor of Circulation and director of the Poly Heart Center at BCU Health in Richmond. Carolyn, we've got a really exciting interview to follow our coffee chat and it's evaluating individuals with low complexity congenital heart disease. We often think of those with high complexity congenital heart disease and looking at their cardiovascular events. We're going to hear a little bit about low complexity congenital heart disease.                                                 Now you've got a paper you wanted to talk about first. Dr Carolyn Lam:                Absolutely. You've got to hang on for that because I'm going to delve into chromatin architecture in heart failure, and it's in this paper from corresponding author Dr Foo from Genome Institute of Singapore.                                                 So, as background, the human genome actually folds in 3D to form thousands of chromatin loops within the nucleus encasing the genes and assists regulatory elements for accurate gene expression control. Now, these physical tethers of loops are anchored by the DNA binding protein CTCF, also known as the weaver of the genome and the cohesion ring complex. Now, the role of CTC in binding and changes in chromatin structure in heart failure are not well understood. Well, until today's paper.                                                 What the author said is they undertook an independent analysis of chromatin organization with mouse pressure overload model of myocardial stress or transverse aortic constriction, and a cardiomyocyte specific knockout of CTCF. So, interestingly, they found that the cardiac chromatin architectural in adult terminally differentiated cardiomyocytes was unchanged in pressure overload from transverse aortic constriction. Now this was completely unlike the CTCF knockout model where they verified that there was generation of vast genome-wide loss of genomic insulation and near complete abolition of the CTCF chromatin loops.                                                 Instead of chromatin rewiring on the scale of that knockout, the myocardial stress response appeared to proceed through enhancer H3K27 acetylation epigenetic changes and gene network co-regulation driven largely by fixed cardiac 3D chromatin architecture. In other words, a stable chromatin architecture really set the stage for accurate enhancer promoter interactions required for basal gene expression control and induction of the classical myocardial stress gene response. Dr Greg Hundley:             So Carolyn, are there therapeutic implications here for this? Dr Carolyn Lam:                Now of course, that was preclinical work, but it really opens the door to consider these epigenetic regulators that control disease expression changes and interacting gene sets in heart as potential future targets for novel heart failure therapy. Dr Greg Hundley:             Very interesting. So, I'm going to review and switch gears a little bit and focus on diabetic cardiomyopathy and mitochondria associated endoplasmic reticulin membranes. And this paper is from Shengnan Wu from the Center for Molecular and Translational Medicine at Georgia State University here in the US in Atlanta, Georgia. So as we all know, mitochondria are essential for cellular energy production, but when they're damaged, they become a major source of reactive oxygen species and pro-apoptotic factors. In particular, increasing evidence suggests that mitochondrial dysfunction is a central event in diabetic cardiomyopathy.                                                 Well, the mitochondria and the endoplasmic reticulum are key players that regulate ma