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.

Keywords: atherosclerosis; cardiovascular disease; diabetes; hypertension; myocardial infarction.

Figure 1.. Increasing lymphatic growth and function to treat metabolic and cardiovascular diseases.

A number of recent studies have highlighted the therapeutic potential of stimulating lymphatic function through lymphangiogenesis, lymphatic growth, and lymphatic remodeling for the treatment of obesity, myocardial infarction, atherosclerosis, and hypertension. (A) Metabolic diseases can systemically impair lymphatic function. Promoting lymphatic growth in metabolic tissues (e.g., skeletal muscle, brown adipose tissue [BAT], and white adipose tissue [WAT]) may resolve insulin resistance and enhance insulin sensitivity to protect against disorders such as obesity. (B) Enhancing lymphangiogenesis after myocardial infarction may clear infiltrating immune cells to reduce the elaboration of pro-inflammatory cytokines as well as decreasing edema, inflammation, and fibrosis to increase functional recovery of the injured heart. (C) Halting the progression or reversing growth of atherosclerotic lesions may depend on increasing lymphatic function in the surrounding tissues by blunting inflammation and reducing cholesterol uptake by immune cell clearance. (D) During hypertension, increased immune cell infiltration and inflammation in renal tissue can contribute to elevations in blood pressure. Augmenting renal lymphangiogenesis may promote immune cell clearance to increase kidney function through sodium excretion to reduce blood pressure.