Insights into pathways of arteriogenesis

The compensatory growth of blood vessels after major arterial occlusions has been termed arteriogenesis. Although having some characteristics in common with angiogenesis, marked differences between both forms of vascular growth exist relating to triggers, underlying mechanisms and physiologic effects. Arteriogenesis describes the remodelling of small interconnecting arterial anastomoses with almost no net blood flow to large functional arteries. It has been shown that growth of these collateral arteries is triggered by physical forces, but does not require hypoxia as a stimulus. In this review we describe an animal model which we used to characterize the role of fluid shear stress for arteriogenesis. Fluid shear stress initiates the activation of endothelial cells and modulates processes which control attraction of circulating cells to the collateral wall. Monocytes were shown to have a pivotal role during arteriogenesis. After entering the vascular wall they function as micro-bioreactors producing cytokines and thereby controlling cell proliferation and remodelling. Furthermore, cell proliferation coincides with the transient dismantling of extracellular structures such as the elastic lamina which is required to provide space for the increasing number of wall cells. After the re-arrangement of wall structures collaterals with large calibres represent functional arteries with the ability to compensate blood flow deficits caused by arterial occlusions. It is therefore questionable, whether there is also a form of de novo collateral artery growth with physiologic relevance.