Presentation description

Heart disease is the leading cause of death in the United States. Systolic heart failure (HF), also known as heart failure with reduced ejection fraction (HFrEF), occurs when the heart is weakened and stretched. Subsequently, the heart cannot pump blood with enough force throughout the body. Systolic HF can be caused by complications such as myocardial infarction (MI), after which fibroblasts are activated and deposit scar tissue comprised of collagen at the infarct site. Persistent fibroblast activation leads to indefinite collagen deposition, impaired tissue contractility, and HF. Adipocyte enhancer binding protein 1 (AEBP1) plays a key role in renal, hepatic, and pulmonary fibrosis by activating tissue-specific fibroblasts. However, its role in cardiac fibrosis is not well understood. Our preliminary results show that increased AEBP1 leads to cardiac fibroblast activation and collagen secretion. We also observed that a global knock-down (KD) of AEBP1 in the heart resulted in decreased fibroblast activation and fibrosis, and improved cardiac function. To understand the specificity of AEBP1 expression in fibroblasts and if we see a similar effect as the global KD, in this study, we aim to KD AEBP1 selectively in cardiac fibroblasts. Here, we induced systolic HF in mice by ligating a coronary artery to simulate a MI. A subset of these mice received a virus that carries a microRNA that will prevent the translation of AEBP1, thus decreasing fibroblast activation and the remaining were left untreated. We expect the treatment group to show a reduction in fibrosis and an improvement in cardiac function.