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 and Duke National University of Singapore. Dr. Greg Hundley: I'm Greg Hundley, associate editor from the Pauley Heart Center at VCU Health in Richmond, Virginia. Dr. Carolyn Lam: Greg, you know I'm vegetarian and any paper on plant-based diet will always interest me, and of course, we have one as a featured paper this week, very interestingly talking about changes in plant-based diet quality, meaning that there could be good plant-based diets and not so good plant-based diets. I mean we all know that potato chips, for example, are still plant-based. But, anyways, so this feature paper discusses the changes in these plant-based diet quality and association with total and cost-specific mortality. Neat, huh? Dr. Greg Hundley: Yeah. I can't wait to hear about that one. I know that's a favorite topic of yours. How about if we have a sip of coffee and jump into our other articles? Dr. Carolyn Lam: Sure. I'm sipping away, and have already picked my first paper. This talks about mutations in plakophilin 2, which are the most common cause of gene-positive familial arrhythmogenic right ventricular cardiomyopathy. Dr. Greg Hundley: No quizzes for me on plakophilin 2, please. Dr. Carolyn Lam: All right, well, let me tell you all about it. Plakophilin 2 is classically defined as a protein of the desmosome, which is an intracellular adhesion structure. Studies though have suggested that plakophilin 2 also translates information at the initiation. Recent studies have also shown that plakophilin 2 translates information initiated at the site of cell to cell contact into intracellular signals that maintain structural and electrical homeostasis. Now, the important thing is that mutations in plakophilin 2 associated with most cases of gene-positive arrhythmogenic right ventricular cardiomyopathy or ARVC. However, the molecular and cellular mechanisms responsible for arrhythmias in ARVC remain unclear. Dr. Carolyn Lam: In today's paper, Doctors Delmar and Cerrone from New York University School of Medicine and their colleagues studied the role of cardiomyocyte plakophilin-2 expression in cardiac function. To do that, they utilized a cardiomyocyte-specific, tamoxifen-activated, plakophilin-2 knockout murine line. They found that loss of plakophilin-2 expression caused, as an early event and predominantly in the right ventricle, a non-transcriptional and likely arrhythmogenic, connexin-43-dependent disruption of calcium homeostasis. Dr. Carolyn Lam: The phenotype included accumulation of calcium in three intracellular compartments, the junctional sarcoplasmic reticulum, the cytoplasm, and the mitochondria. Right ventricular myocytes also showed increased eagerness of ryanodine-receptor-2 channels to release calcium from the sarcoplasmic reticulum. Intrinsic ryanodine-receptor-2 properties were also modified further contributing to the pro-arrhythmogenic state. In summary, the authors postulated that disruption of calcium homeostasis in the right ventricle is a major arrhythmia trigger in patients with ARVC. The data identified both the ryanodine-receptor-2 channel and the connexin-43 hemichannel as targets for antiarrhythmic therapy in this population. Dr. Greg Hundley: Very interesting that ARVC is such a worrisome concern, and gathering this mechanistic information is just so helpful. Dr. Carolyn Lam: Exactly. Dr. Greg Hundley: I have a basic science paper, but it was actually interesting because of the conduct was in many, many human subjects. It emanates from the large Million Veteran Program. There are a whole list of coauthors that are recognized as equal contributors, but Scott Damrauer actually serves as the corresponding author from the VA Medical Center. What it's addressing, about 13% of African American individuals carry two copies of the