Abstract 595: Blocking Cadherin-11 Adhesion After Myocardial Infarction Preserves Cardiac Function

Abstract

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 qPCR and western blot. Results and discussion: Our preliminary results reveal an increase in both survival and cardiac function (ejection fraction) in the treated group relative to controls (A-B). Furthermore, increasing dilation of the left ventricle observed in the control was curtailed in the animals receiving the blocking antibody, resulting in significantly reduced total ventricle volume at 21 days post-MI (C-D). This reduced remodeling was preceded by reduced transcription of IL-6, a pro-inflammatory cytokine, in the antibody treated group three days post-MI (E). Our findings suggest that targeting CDH11-expressing myofibroblasts limits inflammation-driven remodeling while preserving cardiac function. The completion of this project will fully characterize phenotypic changes and tissue remodeling throughout the course of infarct healing, providing new biological insights, and highlighting a potential new treatment strategy for MI.