The lymphatic border patrol outwits inammatory cells in myocardial infarction

Lymphangiogenesis modulates inammation by clearing immune cells in the infarcted heart in a lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1)-dependent process to ameliorate cardiac dysfunction. The lymphatic vascular network plays a fundamental role in cardiac uid regulation: It collects and drains lymph to mediastinal lymph nodes, preventing accumulation of leukocytes, macromolecules, and excessive interstitial uid. The exact role of the lymphatic system in cardiac injury has not been fully established. Using ligation of the left anterior descending coronary artery to obtain myocardial infarction (MI) in mice, Vieira and collaborators elegantly demonstrated that stimulation of the growth of lymphatic vessels-a process known as lymphangiogenesis-markedly improved myocardial function after cardiac ischemia. Lymphangiogenesis induced an active clearance of immune cells within the injured heart, eventually leading to the resolution of the inammatory response, thereby reducing cardiac brosis and pathological remodeling. Mechanistically, the lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1), a protein essential in leukocyte docking, was identied as a key player in these processes. Lyve1 knock-out mice exhibited lower clearance of immune cells after MI compared with wild-type littermates; moreover, Lyve1 ablation triggered a progressive deterioration of myocardial function, accompanied by collagen deposition and scarring, in absence of any lymphatic vessel defects at baseline. These ndings elucidate the functional role of the cardiac lymphatic system after MI. Although the study mainly focused on the regulation of the innate immune response, it is possible that lymphangiogenesis could also regulate the programming of naïve T cells and macrophage polarization. These preclinical results have translational potential, providing the basis for novel therapeutic strategies aimed at enhancing lymphangiogenesis in patients with ischemic heart disease.