Molecular Mechanisms and Therapeutic Strategies Targeting Cardiac Lymphangiogenesis in Heart Failure

Cardiac lymphatics are vital for maintaining tissue-fluid homeostasis and regulating immune response in the heart. Research in recent decades has implicated impaired lymphangiogenesis in the pathophysiology of heart failure following myocardial injury, where it contributes to myocardial oedema, persistent inflammation, and subsequent adverse cardiac remodeling. Growing insight into the molecular aspects of lymphangiogenesis in recent years has opened promising avenues for therapeutic targeting in treating heart failure following myocardial infarction. However, fully harnessing this therapeutic potential requires a deeper understanding of the interactions between the lymphatics and the surrounding microenvironment. Here, we examine how the biology of cardiac lymphatic vasculature offers mechanistic insights for therapeutic targeting in heart failure. In particular, we discuss the mechanism of action underlying the development of cardiac lymphatic vessels. Furthermore, we present an updated synthesis of key signaling pathways, molecular mechanisms, and cellular interactions involved in the intricate cross-talk among cardiac lymphatic endothelial cells, immune cells, and the cardiac extracellular matrix. Overall, we aim to provide a comprehensive framework reflecting current perspectives on how cardiac lymphatic formation is regulated.