Thrombospondin-1 Drives Cardiac Remodeling in Chronic Kidney Disease
Sohel M. Julovi, Katie Trinh, Harry Robertson, Cuicui Xu, Nikita Minhas, Seethalakshmi Viswanathan, Ellis Patrick, John D. Horowitz, Daniel N. Meijles, Natasha M. Rogers
Abstract
Patients with chronic kidney disease (CKD) face a high risk of cardiovascular disease. Previous studies reported that endogenous thrombospondin 1 (TSP1) involves right ventricular remodeling and dysfunction. Here we show that a murine model of CKD increased myocardial TSP1 expression and produced left ventricular hypertrophy, fibrosis, and dysfunction. TSP1 knockout mice were protected from these features. In vitro, indoxyl sulfate is driving deleterious changes in cardiomyocyte through the TSP1. In patients with CKD, TSP1 and aryl hydrocarbon receptor were both differentially expressed in the myocardium. Our findings summon large clinical studies to confirm the translational role of TSP1 in patients with CKD.