Coronary collateral flow and peripheral blood monocyte concentration in patients treated with granulocyte-macrophage colony stimulating factor.

E stablished options for revascularisation of coronary artery disease (CAD) are angioplasty or bypass surgery, both of which are unsuitable in about one in five patients because of the severity of atherosclerosis, comorbidities, or both. An alternative therapeutic option is to promote the endogenous development of collateral vessels. There are three principle ways in which vessel growth can occur: (1) vasculogenesis—this occurs primarily during embryonic development by differentiation of haematopoietic stem cells; (2) angiogenesis—this is the sprouting of new vessels out of existing ones, occurring during embryonic development and under certain conditions in the adult; (3) arteriogenesis—pre-existing collateral arterioles transform into arteries by dilatation, smooth muscle cells and endothelial cells proliferate, and consecutively acquire a typical arterial structure. Angiogenesis is induced by various cytokines, is dependant on ischaemia, and mainly results in high resistance capillaries; true collateral artery growth is temporally and spatially dissociated from ischaemia and results in large interconnecting arterioles which are required for the salvage of myocardium. Aside from their role in defending the host against invading pathogens, monocytes play an important role in building collateral arteries during arteriogenesis. Arteriogenesis is initiated by increased shear forces in pre-existing arterioles (due to an occlusion or narrowing of the main vessel) with subsequent upregulation of adhesion molecules and cytokine production by endothelial cells. Circulating monocytes adhere and migrate into deeper parts of the vessel wall and stimulate vessel growth by releasing cytokines, growth factors, and enzymes such as metalloproteinases. Previous studies, in a model of acute ligation of the femoral artery in mice and rabbits, showed stimulation of arteriogenesis by increased concentrations of blood monocytes and inhibition of collateral artery growth with selective depletion of peripheral blood monocytes. The negative effect was reversed when monocyte depletion was compensated for by an injection of purified monocytes. The purpose of this study was to elucidate whether there is an association between the amount of collateral flow change in response to granulocyte–macrophage colony stimulating factor (GM-CSF) treatment and blood monocyte concentration.