Role of Cardiac Lymphatics in Myocardial Edema and Fibrosis

The cardiac lymphatic network plays a key role in regulation of myocardial extracellular volume and immune cell homeostasis. In different pathological conditions cardiac lymphatics undergo significant remodeling, with insufficient lymphatic function and/or lymphangiogenesis leading to fluid accumulation and development of edema. Additionally, by modulating the reuptake of tissue-infiltrating immune cells, lymphatics regulate immune responses. Available evidence suggests that both edema and inadequate immune response resolution may contribute to extracellular matrix remodeling and interstitial myocardial fibrosis. Interestingly, stimulation of lymphangiogenesis has been shown to improve cardiac function and reduce the progression of myocardial fibrosis during heart failure development after myocardial infarction. This review goes through the available clinical and experimental data supporting a role for cardiac lymphatics in cardiac disease, focusing on the current evidence linking poor cardiac lymphatic transport to the fibrogenic process and discussing potential avenues for novel biomarkers and therapeutic targets to limit cardiac fibrosis and dysfunction. • Structural and functional alterations in cardiac lymphatics occur in both acute and chronic cardiac diseases . • Insufficient or maladaptive lymphatic remodeling in the heart leads to chronic edema and inflammation. • Edema and inflammation trigger development of myocardial interstitial fibrosis by activating fibroblasts • The potential clinical usefulness of cardiac lymphangiogenic therapies merits further studies.