Pharmaceutical interventions to influence arteriogenesis: new concepts to treat ischemic heart disease

Despite the technical progress in interventional techniques to overcome the harmful effects of ischemic heart disease there is still an urgent need for alternative, pharmaceutical treatment modalities. Exogenous stimulation of vessel growth, i.e. vasculogenesis, angiogenesis or arteriogenesis serves as a promising strategy to restore blood flow to the jeopardized tissue regions downstream of arterial stenosis or occlusion. While vasculogenesis is defined as the arrangement of angioblasts during prenatal development creating the first vascular network, angiogenesis and arteriogenesis refer to important adaptive mechanisms in the adult organism. Angiogenesis, neo-formation of capillaries, is a key process in many different physiological and pathophysiological events where improvement of microvascular function and tissue nutrition is needed (e.g. wound healing, tumor growth). In contrast to this capillary sprouting, the term arteriogenesis refers to the development of large caliber collateral arteries. Under conditions of increasing shear stress, anastomoses between interconnected perfusion territories can undergo adaptive enlargement, developing into a functional network of collateral arteries, natural bypasses able to maintain sufficient blood flow and compensating for the gradual occlusion of a large artery (e.g. in the coronary circulation). However, in most cases arteriogenesis does not proceed as fast as the stenosis progresses and infarction and tissue necrosis results. A well-developed collateral network is an important protective factor for the occurrence of ischemic events and therefore pharmaceutical acceleration and stimulation of arteriogenesis in patients represents an eminent aim for the future. This review focuses on the basic mechanisms of arteriogenesis, the recent progresses in translating these insights into the clinical situation and the problems yet to be solved.