The cardiac lymphatic system stimulates resolution of inflammation following myocardial infarction

J Clin Invest. 2018 Aug 1;128(8):3402-3412. doi: 10.1172/JCI97192. Epub 2018 Jul 9.


Myocardial infarction (MI) arising from obstruction of the coronary circulation engenders massive cardiomyocyte loss and replacement by non-contractile scar tissue, leading to pathological remodeling, dysfunction, and ultimately heart failure. This is presently a global health problem for which there is no effective cure. Following MI, the innate immune system directs the phagocytosis of dead cell debris in an effort to stimulate cell repopulation and tissue renewal. In the mammalian adult heart, however, the persistent influx of immune cells, coupled with the lack of an inherent regenerative capacity, results in cardiac fibrosis. Here, we reveal that stimulation of cardiac lymphangiogenesis with VEGF-C improves clearance of the acute inflammatory response after MI by trafficking immune cells to draining mediastinal lymph nodes (MLNs) in a process dependent on lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1). Deletion of Lyve1 in mice, preventing docking and transit of leukocytes through the lymphatic endothelium, results in exacerbation of chronic inflammation and long-term deterioration of cardiac function. Our findings support targeting of the lymphatic/immune cell axis as a therapeutic paradigm to promote immune modulation and heart repair.

Keywords: Cardiovascular disease; Inflammation; Vascular Biology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement*
  • Heart Failure / genetics
  • Heart Failure / metabolism
  • Heart Failure / pathology
  • Inflammation / genetics
  • Inflammation / metabolism
  • Inflammation / pathology
  • Leukocytes / metabolism*
  • Leukocytes / pathology
  • Lymphangiogenesis*
  • Lymphatic System / metabolism*
  • Lymphatic System / pathology
  • Mice
  • Mice, Knockout
  • Myocardial Infarction / genetics
  • Myocardial Infarction / metabolism*
  • Myocardial Infarction / pathology
  • Myocytes, Cardiac / metabolism*
  • Myocytes, Cardiac / pathology
  • Vascular Endothelial Growth Factor C / genetics
  • Vascular Endothelial Growth Factor C / metabolism
  • Vesicular Transport Proteins / genetics
  • Vesicular Transport Proteins / metabolism


  • LYVE1 protein, mouse
  • Vascular Endothelial Growth Factor C
  • Vesicular Transport Proteins
  • vascular endothelial growth factor C, mouse