Cardiac Lymphatics – A New Avenue for Therapeutics?

Cardiac lymphatic endothelial cells originate from multiple sources. In the heart, they form a network of capillary lymphatic vessels and larger collector lymphatics that drain fluid, macromolecules, and inflammatory cells. The role of lymphatic vessels in chylomicron metabolism is well-established, and lymphatics are also required for RCT. Therefore, lymphatics may play even a more significant role in lipid and lipoprotein metabolism than previously thought. Lymphangiogenic therapy may become a useful option for the treatment of cardiovascular diseases such as atherosclerosis and myocardial ischemia. In addition, anti-lymphangiogenic therapy could be utilized to resolve inflammatory reactions in cardiac allografts. Recent progress in lymphatic vessel biology and in novel imaging techniques has established the importance of the lymphatic vasculature as part of the cardiovascular system. The lymphatic vessel network regulates many physiological processes important for heart function such as fluid balance, transport of extravasated proteins, and trafficking of immune cells. Therefore, lymphangiogenic therapy could be beneficial in the treatment of cardiovascular diseases, for example by improving reverse cholesterol transport (RCT) from atherosclerotic lesions or by resolving edema and fibrosis after myocardial infarction. In this review we first describe recent findings on the development and function of cardiac lymphatic vessels, and subsequently focus on the prospects of pro- and anti-lymphangiogenic therapies in cardiovascular diseases. Recent progress in lymphatic vessel biology and in novel imaging techniques has established the importance of the lymphatic vasculature as part of the cardiovascular system. The lymphatic vessel network regulates many physiological processes important for heart function such as fluid balance, transport of extravasated proteins, and trafficking of immune cells. Therefore, lymphangiogenic therapy could be beneficial in the treatment of cardiovascular diseases, for example by improving reverse cholesterol transport (RCT) from atherosclerotic lesions or by resolving edema and fibrosis after myocardial infarction. In this review we first describe recent findings on the development and function of cardiac lymphatic vessels, and subsequently focus on the prospects of pro- and anti-lymphangiogenic therapies in cardiovascular diseases. a progressive disease characterized by accumulation of cholesterol, extracellular matrix, fibrosis, calcium deposits and inflammatory cells within the arterial wall. the abnormal accumulation of fluid in the interstitium leading to tissue swelling and pain. a small, apolipoprotein A (APOA)-rich lipoprotein responsible for RCT of cholesterol from extrahepatic tissues to liver. the formation of new lymphatic vessels from pre-existing lymphatic vessels specialized form of epithelial cells that line the lymphatic vessels. an organ linked to lymphatic vessels. It is full of immune cells that recognize foreign particles and remove bacteria, viruses, and toxins as well as cancer cells from the body. a white blood cell that engulfs and digests microbes, cellular debris, and any foreign substances. Macrophages can also act as antigen-presenting cells to activate immune responses. cardiac muscle damage and/or necrosis as a result of occlusion of a coronary artery caused by atherosclerotic plaques. movement of cholesterol from peripheral tissues back to the liver via plasma lipoproteins. a tyrosine kinase receptor that binds vascular endothelial growth factors C and D. It is essential for the development and maintenance of lymphatic vessels.