Cardiac lymphatics: state of the art

The beneficial role of cardiac lymphatics in health and disease has begun to be recognized, with both preclinical and clinical evidence demonstrating that lymphangiogenesis is activated in cardiovascular diseases. This review aims to summarize our current understanding of the regulation and impact of cardiac lymphatic remodeling during development and in adult life, highlighting emerging concepts regarding distinguishing traits of cardiac lymphatic endothelial cells (LEC).

Genetic lineage-tracing and clonal analyses have revealed that a proportion of cardiac LECs originate from nonvenous sources. Further, these sources may vary between different regions of the heart, and could translate to differences in LEC sensitivity to molecular regulators. Several therapeutic approaches have been applied to investigate how lymphatics contribute to resolution of myocardial edema and inflammation in cardiovascular diseases. From these studies have emerged novel insights, notably concerning the cross-talk between lymphatics and cardiac interstitial cells, especially immune cells.

Recent years have witnessed a significant expansion in our knowledge of the molecular characteristics and regulation of cardiac lymphatics. The current body of work is in support of critical contributions of cardiac lymphatics to maintain both fluid and immune homeostasis in the heart.