The pathophysiology of the collateral circulation (arteriogenesis)

Since the mid 1980s a new strategy is coming from bench to bedside termed angiogenesis. This process involves sprouting of capillaries and finally results in newly developed microvessels which belong to the capillary level. Importantly these newly formed capillary tubes lack vascular smooth muscle cells, they are not surrounded by mural cells and are fragile and prone to rupture. Therefore these networks remain susceptible to hypoxic regulation, fail to become remodelled and are unable to sustain proper circulation: they cannot adapt to changes in physiological demands of blood supply. Since atherosclerosis affects large conductance arteries, capillary sprouting from compromised vessels cannot provide an adequate supply of blood flow to the endangered tissue. However, the body provides a natural system of pre-existing collateral arteries, which may bypass sites of arterial occlusion. These vessels can dramatically increase their lumen by growth so as to provide enhanced perfusion to the jeopardized ischaemic regions. This process - termed arteriogenesis - finally results in fully functional and structurally normal arteries which can ameliorate the ensuing detrimental effects of vessel obstruction in many regions of the body. Hallmarks of arteriogenesis are increased levels of shear forces (rather than ischaemia), the invasion of circulating monocytes (and their pluripotent precursors), and the substrates of arteriogenesis are pre-existing collateral arterioles.