Is capillary sprouting enough?

Abstract

After birth, the formation of new blood vessels takes place via angiogenesis of arteriogenesis. Angiogenesis is defined as capillary sprouting and results in higher capillary density. It is an important component of various normal and pathological conditions such as wound healing, fracture repair, folliculogenesis, ovulation, and pregnancy. These periods of angiogenesis are tightly regulated. However, if not properly controlled, angiogenesis can also represent a significant pathogenic component of tumor growth and metastasis, rheumatic arthritis, and retinopathies. It is important to recognize that these newly formed capillary tubes lack vascular smooth muscle cells. Any developing new network of endothelial tubes (sprouting capillaries) that is not surrounded by mural cells is fragile and prone to rupture, remains susceptible to hypoxic regulation, fails to become remodeled, and is unable to sustain proper circulation: it cannot adapt to changes in physiological demands of blood supply.

Arteriogenesis defines the growth of arteries from preexisting arterioles and is potentially able to alter significantly the outcome of coronary and peripheral artery disease. Arteriogenesis is by far the most efficient adaptive mechanism for the survival of ischemic limbs or internal organs, like heart and brain, because of its ability to conduct, after adaptive growth, relatively large blood volumes per unit of time. An increased number of capillaries, the result of stimulated angiogenesis, is unable to do that. Arteriogenesis differs from angiogenesis in several aspects, the most important being the dependence of angiogenesis on hypoxia and the dependance of arteriogenesis on inflammation. However, angiogenesis and arteriogenesis share several mechanisms of action, like their dependence on growth factors. Whereas angiogenesis can be largely explained by the actions of VEGF, arteriogenesis is probably a multifactorial process where several growth factors are orchestrated. The role of VEGF in arteriogenesis is not clear, but a chemoattractive role for monocytes and hence an indirect contribution is imaginable.