Arteriogenesis: basic mechanisms and therapeutic stimulation

Pharmacological attempts to stimulate the growth of collateral arteries (arteriogenesis) are evolving towards a new treatment option for patients with vascular occlusive diseases. This enlargement of small pre-existing anastomoses towards large conductance arteries takes place independent of local oxygen tension and is driven by changes in luminal shear stress and infiltration of circulating cells. With the increasing knowledge regarding the distinct differences between capillary sprouting (angiogenesis) and arteriogenesis, several cytokines and growth factors have been demonstrated to stimulate the growth of arterial blood vessels in preclinical models of vascular disease. However, the translation towards clinical practice remains difficult and first in-man trials show limited success. Intensive research especially regarding new drug delivery platforms and the potentially serious side effects of pro-arteriogenic therapeutics is warranted before stimulation of arteriogenesis could become a significant treatment option for vascular occlusive diseases. This review focuses on the recent advances in the field of collateral artery growth. In addition, possible means to overcome the hurdles that have hampered the clinical implementation of pro-arteriogenic therapies will be discussed.