The role of platelets in lymphangiogenesis and neoangiogenesis

Abstract

During the developmental stages, when the primary lymph sac arises from the cardinal vein, podoplanin in lymphatic endothelial cells (LECs) activates platelets by binding to CLEC-2, which facilitates blood/lymphatic vessel separation. One of the mechanisms for this process is that granule contents from activated platelets inhibit the migration and proliferation of LECs, thereby facilitating separation of the vessels. Angiogenesis consists of several steps, including activation of endothelial cells (ECs), migration to the site of the vessel branch, proliferation, and formation of tube-like structures. Granule contents released from activated platelets, including VEGF and FGF, are required for EC proliferation. On the other hand, direct contact between platelets and ECs via platelet membrane proteins, including GPIba and α IIb β 3 , prompts angiogenesis by stabilizing developing vessels. Platelets also play a crucial role in maintaining the vascular integrity of high endothelial venules in lymph nodes and inflammatory vessels via the podoplanin receptor CLEC-2 and the collagen receptor glycoprotein VI. Platelets also regulate cerebrovascular patterning and integrity during development via CLEC-2 and podoplanin in neuroepithelial cells. Thus, platelets play a role, not only in thrombosis and hemostasis, but also in lymphangiogenesis, angiogenesis, and maintenance of vascular integrity.