Blocking Cadherin-11 Adhesion After Myocardial Infarction Preserves Cardiac Function

Introduction: Over one million Americans experience myocardial infarction (MI) every year, and the resulting scar and subsequent cardiac fibrosis contribute to heart failure and death. The cells primarily responsible for scar formation and cardiac fibrosis are cardiac fibroblasts (CFs), which differentiate into active myofibroblasts in response to injury, expressing a specialized adhesion protein: cadherin-11 (CDH11). CDH11 has recently been shown to contribute to inflammation and fibrosis in both rheumatoid arthritis and pulmonary fibrosis; therefore we hypothesized that blocking CDH11 adhesion after MI would reduce inflammation-driven infarct expansion and fibrotic remodeling to improve functional outcomes in mice. Methods: MI was induced in mice by ligation of a coronary artery, and mice were injected with a functional blocking antibody against CDH11 or a control IgG for 21 days. We assessed dynamic cardiac function with echocardiogram and measured changes in protein transcription and expression by qPC...