Abstract 644: Enhancing Lymphangiogenesis Ameliorates Chronic Heart Failure

Abstract

Previous studies have indicated that cardiac lymphatics are involved in the pathogenesis of acute cardiac injuries. However, the role of cardiac lymphatics in the pathogenesis of chronic heart failure remains unclear. The goal of this study is to investigate the role of cardiac lymphatics in the development of chronic heart failure, and to test the hypothesis that improving lymphatic vascular function will have therapeutic benefits in chronic heart failure. First, we characterized lymphatic endothelial marker expression in human hearts from normal or heart failure patients, and a trend towards reduced lymphatic marker expression was observed. These data suggested that lymphatic vessels may be impaired in chronic heart failure. To test this hypothesis further, angiotensin II infusion was used to induce cardiac dysfunction and hypertrophy in mice. Using lymphangiography, we discovered impaired lymphatic transport in angiotensin II-infused mouse hearts compared with control mouse hearts, suggesting impairments in cardiac lymphatic function. Interestingly, when the angiotensin II infused mice were co-administered VEGFCc156s protein to enhance lymphangiogenesis and improve lymphatic vascular function, the VEGFCc156s-treated mice demonstrated improved cardiac function and reduced cardiac hypertrophy compared with angiotensin II infused mice, indicating a potential beneficial effect of VEGFCc156s treatment on angiotensin II-induced cardiac dysfunction and hypertrophy. Overall, these results demonstrate that cardiac lymphatic vessels were impaired in chronic heart failure, and improving lymphatic vascular function may have therapeutic effects on chronic heart failure. The outcome of the study may provide new insights into developing new therapeutics for chronic heart failure.