1. From avascular to vascular It is clear that for vasculogenesis and angiogenesis to effectively proceed during physiological and pathological From the earliest stages, the embryo develops in the conditions, it is essential that a complex array of anabsence of vascularization, receiving its nutrition by giogenic and anti-angiogenic factors, interacting with diffusion [1]. In an ordered and sequential manner, how- multiple cells and tissues, be tightly regulated. Although ever, the embryo rapidly transforms into a highly vascular endothelial cells have attracted the most attention, they organism, survival being dependent on a functional, com- alone cannot complete the process of vessel growth and plex network of capillary plexuses and blood vessels. development, as peri-endothelial cells and matrix com-‘Vasculogenesis’ refers to the initial events in vascular ponents play essential roles. Innovative gene technologies growth in which endothelial cell precursors (angioblasts) and advances in animal modeling have enabled research migrate to discrete locations, differentiate in situ and scientists to make major advances in understanding the assemble into solid endothelial cords, later forming a mechanisms of blood vessel growth. The ultimate theraplexus with endocardial tubes (Fig. 1). The subsequent peutic goals, which are to mitigate against angiogenesis growth, expansion and remodeling of these primitive during pathological processes such as inflammation and vessels into a mature vascular network is referred to as tumorigenesis, and to enhance angiogenesis to prevent ‘angiogenesis’(Fig. 1). This process is characterized by a and/or treat ischemic events, have become realizable at the combination of sprouting of new vessels from the sides clinical level, and thus caught the imagination and attenand ends of pre-existing ones, or by longitudinal division tion of all those involved in health care and research [3, 4]. of existing vessels with periendothelial cells (intussuscep- In the past 15–20 years, major breakthroughs have resulted tion), either of which may then split and branch into in the emergence of useful paradigms to help explain precapillary arterioles and capillaries. Depending on the vasculogenesis and angiogenesis. This review provides an ultimatefatewithrespecttothetypeofvessel (artery, vein, update on some of the basic molecular mechanisms capillary) and vascular bed, activated endothelial cells that governing how endothelial cells, smooth muscle cells, are migrating and proliferating to form new vessels, matrix molecules, and several critical receptors and their forming anastomotic connections with each other, become ligands, interact with each other to form blood vessels. As variably surrounded by layers of periendothelial cells— will become evident, the rapid growth in our understanding pericytes for small vessels and smooth muscle cells for has provided scientists with new and exciting potential large vessels (‘vascular myogenesis’)(Fig. 1)[2]. During options to address the therapeutic goals. However, there this dynamic period, extracellular matrix produced by are still many aspects of vasculogenesis and angiogenesis mural cells, serves to stabilize the network. Finally, further that remain challenges to our knowledge. These are being functional modifications of larger arteries occur during met with remarkable rapidity.‘arteriogenesis’ as a thick muscular coat is added, concomitant with acquisition of viscoelastic and vasomotor