The (PROX1) transcription factor, integral membane glycoprotein podoplanin (PDPN),

The human body has two circulatory systems, the cardiovascular system and the lymphatic system. In contrast to the blood vascular circulation, the lymphatic system forms a unidirectional transit pathway from the extracellular space to the venous system. This system is actively regulating the homesostasis of tissue flow, the transit of antigen presenting cells, the absorption of gastrointestinal lipids, the transit of lymphocytes to lymphoid organs and to systemic circulation. Below we will discuss recent medical research involving the lymphatic system in the pathology of cardiovascular diseases such as obesity, dyslipidemia, inflammation, arteriosclerosis, hypertension and cardiac infarction and metabolic disease.For many years lymphatic vessels were ignored in research, but during the 21st century research on this topic began to flourish, where through molecular genetic studies discovered more than 50 genes involved in the specification, expansion and maturation of lymphatic vessels. However, in the past, vascular endothelial growth factor (VEGFR) -3 receptors, prospero homeobox 1 (PROX1) transcription factor, integral membane glycoprotein podoplanin (PDPN), and lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1) as lymphatic-specific markers had already been identified. The lymphatic system has ceased to be a passive system, to become an active system because is actively regulating numerous physiological and pathological processes.But how does the lymphatic system influence the pathogenesis of cardiovascular diseases, first we will analyze:LymphedemaIt is the abnormal accumulation of the interticial liquid produced by an alteration of the lymphatic drainage. The linfedemas are classified in primary or inherited that are the result of defects in the genes involving most often the VEGFC/ VEGFR3 signaling axis in the development of the lymphatic vessels. Secondary or acquired lymphedemas arise from damage or physical obstruction of the lymphatic vessels or lymph node (NL).The latest studies reveal that in a postmastectomy lymphedema, the functional lymphatic network can be restored in the damaged areas with the concomitant autologous NL transplant, and with the overexpression of local and transient VEGFC that has been validated in large animals and that now advances to clinical trials for the treatment of postmastectomy lymphedema.ObesityWe know that excess body weight is the most important risk factor that contributes to cardiovascular diseases. According to studies at the beginning it was thought that the malfunction of the lymphatic vessels can be the cause of obesity, the study was done in Prox1 mice who developed obesity without changes in the intake or energy expenditure, but then surprisingly discovered the deficiency of the VEGFC gene had no effect on the lymphatic vasculature in the skin, trachea or NL, but caused a slow regression of the intestinal lymphatic vessels causing the atrophy of the intestinal lymph nodes reduced the absorption of lipids, increasing the excression of lipids in stool, counteracting obesity and improving glucose metabolism. These findings could open possibilities for the development of new drugs to treat dyslipidemia and obesity.Inflammation / Trasnplant RejectionInflammation is part of a complex biological response associated with the protection of tissues against harmful stimuli such as pathogens, damaged cells and irritants. During inflammation there is a greater demand for lymphatic tissue where it is suggested that inflammation-associated lymphangiogenesis (IAL) is profoundly altering the course of inflammation and tissue repair. This can be seen particularly with the rejection of transplants that is associated with a very extensive lymphangiogenic response. Even more it was discovered that if the signaling of the VEGFR3 is blocked, the survival of the graft increases, because it would be modulating the passage of immune cells. In other words, antilinfangiogenic therapy increases the survival of grafts.Atherosclerosis / Myocardial Infarction (MI) Atherosclerosis involves a chronic inflammatory disease of the arterial wall. To understand scientific advances we must remember that the process of multiple cholesterol mobilization from extravascular tissues to biliary and non-biliary excretion is called reverse cholesterol transport (RCT), where the elimination of cholesterol is produced by the macrophages, which After going through a series of processes HDL is formed, it is important to mention this HDL because it was shown that HDL mainly uses lymphatic vessels for blood flow, then it was discovered that if lymphangiogenesis is induced by the administration of VEGFC improve lymphatic function improving decreased footpad cholesterol content. In general, these data indicate that the RCT is critically dependent on the lymphatic vessels and that the venous system is not sufficient to maintain an RCT. In addition, inducing lymphangiogenesis could be a strategy to improve the RCT. This could be especially important in the case of hypercholesterolemia and obesity that directly alter the function of the lymphatic vessel.1The most important complication of atherosclerosis is acute coronary syndrome, often culminating to myocardial infarction (MI). In recent studies it was shown that after MI, cardiac lymphatic vessels undergo a profound lymphangiogenic response and that ectopic stimulation of VEGFC increases their response, resulting in a transient improvement in post-MI cardiac function. Therefore, in conclusion inducing lymphangiogenesis could provide a pathway for the flow of inflammatory cells to favor the healing of wounds within the injured adult heart.