Authors: Meiling Melzer, Dina Hassan, David Beier, Pampee P Young, Sarika Saraswati
Published: 2020-10-27
DOI: 10.1161/res.127.suppl_1.482
Source: Full article
Almost 6.5 million people in United States suffer from heart failure (HF). Diastolic HF following non-ischemic cardiac insult is a progressive condition with limited effective therapies underscoring the urgency to invest in identifying novel therapeutic targets for treatment. Reactive fibrosis in response to pathological stress is one of the major causes of diastolic HF. Emerging data suggest an association of systemic inflammation with reactive fibrosis and HF. Canonical Wnt/beta-catenin signaling has been linked to HF and fibrosis with limited understanding of the precise cellular and molecular mechanism. We utilized thoracic aortic constriction (TAC), a well-defined model of HF, to study Wnt signaling mediated reactive fibrosis. TAC was induced in a transgenic mouse model with stabilized beta-catenin (Wnt signaling) in fibroblasts (Bcat/Postn). Wnt activation following TAC resulted in increased maladaptive reactive fibrosis, HF marker ANP, and cardiac hypertrophy with preserved Ejection Fraction (pEF) suggesting Wnt-mediated progression of diastolic heart failure with pEF. TAC also resulted in increased macrophage activation and recruitment of CD8+ cytotoxic T-cells.