Description
Normal tissue function depends on a regular supply of oxygen through the blood vessels. Understanding the formation of blood vessels has become the focus of a major research effort throughout the last decade. Vasculogenesis in the embryo is the process by which new blood vessels are generated de novo from primitive precursor cells. Angiogenesis is the process of new blood vessel formation from pre-existing vasculatures. It plays an essential role in development, normal tissue growth, wound healing, the female reproductive cycle (placental development, ovulation, corpus luteum) and also plays a major role in various diseases. Special interest is focused on tumor growth, since tumors cannot grow more than a few millimeters in size without developing a new blood supply. This process is described as tumor angiogenesis which is also essential for the spread and growth of tumor cell metastasis. One of the key molecules for angiogenesis and for the survival of the endothelium is vascular endothelial growth factor (VEGF-A). It is a specific endothelial cell mitogen and a strong vascular permeability factor (VPF). VEGF-A is a heparin-binding glycoprotein, secreted as a homodimer of 45 kDa by many different cell types. VEGF-A also causes vasodilation through the nitiric oxide synthase pathway in endothelial cells and can activate migration in monocytes. Many different splice variants of VEGF-A have been described, but VEGF165 is the most predominant protein and anchors with its heparin binding domain to extracellular matrix and to heparin sulfate. During the past few years, several other members of the VEGF family have been cloned, including VEGF-B, -C- and -D. In terms of vascular angiogenesis, which mainly is regulated by VEGF-A, lymphangiogenesis is mainly regulated by VEGF-C and -D