Role of monocytes and macrophages in adult angiogenesis: A light at the tunnel's end

In spite of sustained efforts, there are still gaps in our understanding of angiogenesis as it takes place in vivo. Older observations and a number of recent developments strongly involve the blood mononuclear cell population, collectively known as monocytes (MC), in the normal and pathological adult angiogenesis. An emerging paradigm should eventually incorporate the established biochemical cross talk between MC and their descendents, tissular macrophages (Mph), and the endothelial cells (EC); additionally, it should account for both the intercellular cooperation at the morphological level and the phenotypic overlap between the two cell populations. This focused review puts together the pieces of this puzzle in such a way as to suggest an alternative angiogenic model applicable to adult animals, and particularly to pathological conditions. A working hypothesis is put forward, which is centered on the preformation of capillary lumen as a tunnel drilled by penetrating MC/Mph. The tunnels may be colonized in a later stage by sprouts, circulating progenitor endothelial cells (CPEC) or transdifferentiated EC. Thus, MC/Mph are suggested to be included among the targets of therapeutic manipulation of angiogenesis.