Functions and Regeneration of Mature Cardiac Lymphatic Vessels in Atherosclerosis, Myocardial Infarction, and Heart Failure.

Cardiac lymphatic vessels play a vital role in maintaining cardiac homeostasis both under physiological and pathological conditions. Clearer illustration of the anatomy of cardiac lymphatics has been achieved by fluorescence exhibition comparing to dye injection. Besides, identification of specific lymphatic markers in recent decades paves the way for researches in development and regeneration of cardiac lymphatics, such as VEGF-C/VEGFR-3, EphB4/ephrin-B2, Prox-1, Podoplanin, and Lyve-1. Knocking out each of these markers in mice model also reveals the signaling pathways instructing the formation of cardiac lymphatics. In the major cardiovascular disease series of atherosclerosis, myocardial infarction (MI), and heart failure, cardiac lymphatics regulate the transportation of extravasated proteins and lipids, inflammatory and immune responses, as well as fluid balance. Elementary intervention methods, such as lymphatic factor protein injection VEGF-C, are applied in murine MI models to restore or enhance functions of lymphatic vessels, achieving improvements in cardiac function. Also, data from our laboratory showed that intramyocardial EphB4 injection also improved lymphatic regeneration in mouse MI model. Therefore, we believe that enhancing functions and regeneration of mature cardiac lymphatic vessels in cardiovascular diseases is of great potential therapeutic meaning in the future.