title: Diabetic microvascular complications and growth factors.
abstract: Diabetes mellitus is associated with typical patterns of long term vascular complications which vary with the organ involved. The microvascular kidney disease (Olgemoller and Schleicher, 1993) is characterized by thickening of the capillary basement membranes and increased deposition of extracellular matrix components (ECM), while loss of microvessels with subsequent neovascularisation is predominant in the eye and peripheral nerves. On the other hand macrovascular disease is characterized by accelerated atherosclerosis. These complications are dependent on long term hyperglycemia. Specific biochemical pathways linking hyperglycaemia to microvascular changes were proposed: the polyol pathway (Greene et al., 1987), non-enzymatic glycation of proteins (Brownlee et al., 1988), glucose autooxidation and oxidative stress (Hunt et al., 1990), hyperglycemic pseudohypoxia (Williamson et al., 1993) enhanced activation of protein kinase C by de novo-synthesis of diacyl glycerol (Lee et al., 1989; DeRubertis and Craven 1994) and others. These pathways are not mutually exclusive (Larkins and Dunlop, 1992; Pfeiffer and Schatz, 1992). They may be linked to alterations in the synthesis of growth factors particularly since atherosclerosis and angioneogenesis are associated with increased proliferation of endothelial and smooth muscle cells. Increased synthesis of ECM components is stimulated by growth factors like transforming growth factor beta (TGF beta) (Derynck et al., 1984) and insulin-like growth factor I (IGF-I) (Moran et al., 1991). This review will summarize some of the recent evidence for an involvement of growth factors in diabetic vascular complications and will attempt to assign their emergence in the sequence of events leading to vascular complications.
authors.affiliation: Medizinische Klinik und Poliklinik, Ruhr-Universität, Bochum, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Pfeiffer
authors.forename: H
authors.initials: H
authors.lastname: Schatz
mesh_terms: D000818:Animals; D001161:Arteriosclerosis / Q000378:metabolism* / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000378:metabolism* / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000378:metabolism / Q000503:physiopathology; D003930:Diabetic Retinopathy / Q000378:metabolism / Q000503:physiopathology; D004815:Epidermal Growth Factor / Q000652:urine; D016222:Fibroblast Growth Factor 2 / Q000502:physiology; D013006:Growth Hormone / Q000502:physiology; D006133:Growth Substances / Q000096:biosynthesis* / Q000502:physiology; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism / Q000503:physiopathology; D007333:Insulin Resistance; D007334:Insulin-Like Growth Factor I / Q000502:physiology; D011986:Receptors, Somatotropin / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
chemical_list: D006133:Growth Substances; D011986:Receptors, Somatotropin; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016222:Fibroblast Growth Factor 2; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone