Promoting Lymphangiogenesis and Lymphatic Growth and Remodeling to Treat Cardiovascular and Metabolic Diseases

Abstract

Lymphatic vessels are low-pressure, blind-ended tubular structures that play a crucial role in the maintenance of tissue fluid homeostasis, immune cell trafficking, and dietary lipid uptake and transport. Emerging research has indicated that the promotion of lymphatic vascular growth, remodeling, and function can reduce inflammation and diminish disease severity in several pathophysiologic conditions. In particular, recent groundbreaking studies have shown that lymphangiogenesis, which describes the formation of new lymphatic vessels from the existing lymphatic vasculature, can be beneficial for the alleviation and resolution of metabolic and cardiovascular diseases. Therefore, promoting lymphangiogenesis represents a promising therapeutic approach. This brief review summarizes the most recent findings related to the modulation of lymphatic function to treat metabolic and cardiovascular diseases such as obesity, myocardial infarction, atherosclerosis, and hypertension. We also discuss experimental and therapeutic approaches to enforce lymphatic growth and remodeling as well as efforts to define the molecular and cellular mechanisms underlying these processes.

CCR2 inhibitor strengthens the adiponectin effects against myocardial injury after infarction

“…Promoting lymphangiogenesis and lymphatic growth could remodel the infarcted area and border zone to treat cardiovascular and metabolic diseases. 39 LYVE1+ macrophages can interplay with lymphatic endothelial cells to support homeostasis and promote lymphangiogenesis. In addition, LYVE1+ macrophages play a critical role as a type of cardiac interstitial macrophage to control the ECM in order to promote macrophage M2 polarization and decrease the adverse remodeling after myocardial infarction.…”

“…Promoting lymphangiogenesis and lymphatic growth could remodel the infarcted area and border zone to treat cardiovascular and metabolic diseases 39 . LYVE1+ macrophages can interplay with lymphatic endothelial cells to support homeostasis and promote lymphangiogenesis.…”

Advances in lymphedema: An under-recognized disease with a hopeful future for patients

“…26 The role of lymphatics in cardiovascular disease has just recently been explored. 123 Improved understanding and interventions directed at the central lymphatic system and thoracic duct may offer new insights and therapies for chylothorax, refractory ascites, and congestive heart failure. 124,125…”

Role of the Lymphatics in Cardiac Disease

“…The disease is initiated by the accumulation of LDL (low-density lipoprotein), and its subsequent oxidation (oxidized LDL), which activates endothelial cells and recruits macrophages to engulf the oxidized LDL. 39 These macrophages then produce inflammatory cytokines and contribute to the formation of plaques that consist of fat, cholesterol, and immune cells. 40 The associated chronic inflammatory response renders plaques vulnerable to rupture, placing downstream tissue at significant risk of injury.…”