title: Impaired collateral vessel development in diabetes: potential cellular mechanisms and therapeutic implications.
abstract: The formation of coronary collateral vessels is a compensatory mechanism secondary to repetitive or chronic myocardial ischemia. During the past three decades the functional and prognostic benefit of such collateral vessels has been established. There are large interindividual differences in the number and extent of collateral vessels that may be explained by differences in the anatomic situation or by differences in the individual capacity to develop functional collateral vessels. Diabetes mellitus has recently been identified as one of the first negative predictors of collateral vessel formation. Novel molecular approaches have helped to improve our understanding of the process of collateral vessel formation in recent years. Besides the process of true angiogenesis, i.e. the formation of new capillaries out of preexisting ones, the formation of a collateral circulation is largely based on the growth of preexisting arterioles (collateral vessels or anastomoses) named arteriogenesis. One important feature of arteriogenesis is the infiltration of monocytes into the growing collateral vessel. Our group shows that the ability of monocytes to migrate towards a gradient of VEGF-A is severely impaired in diabetic individuals, and this impaired response seems to be secondary to a signal transduction defect within the monocyte. In this review the pathophysiology of diabetes-related monocyte dysfunction and the potential role of VEGF-A in collateral vessel formation are discussed.
authors.affiliation: Department of Internal Medicine II (Cardiology), Ulm University Medical Center, Robert-Koch-Strasse 8, 89081, Ulm, Germany. johannes.waltenberger@medizin.uni-ulm.de
authors.forename: J
authors.initials: J
authors.lastname: Waltenberger
mesh_terms: D000368:Aged; D000818:Animals; D002465:Cell Movement; D003097:Collateral Circulation; D003327:Coronary Disease / Q000503:physiopathology*; D016207:Cytokines / Q000378:metabolism; D003920:Diabetes Mellitus / Q000503:physiopathology*; D016228:Endothelial Growth Factors / Q000378:metabolism / Q000627:therapeutic use; D006801:Humans; D008222:Lymphokines / Q000378:metabolism / Q000627:therapeutic use; D009000:Monocytes / Q000502:physiology; D018919:Neovascularization, Physiologic; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D042442:Vascular Endothelial Growth Factors
chemical_list: D016207:Cytokines; D016228:Endothelial Growth Factors; D008222:Lymphokines; D011518:Proto-Oncogene Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D020794:Receptor Protein-Tyrosine Kinases; D040281:Vascular Endothelial Growth Factor Receptor-1