title: Human endothelial cells are defective in diabetic vascular disease.
abstract: Diabetic vascular disease is characterized pathologically by endothelial cell (EC) hyperplasia and basement membrane (BM) thickening. One key question regarding the pathogenesis of diabetic vascular disease is whether the EC or BM or both are primarily defective and responsible for these pathological changes. Previous studies, which took the approach of creating artificial diabetic conditions, have been inconclusive. It is known, however, that the extracellular matrix may be altered by glycosylation as a result of hyperglycemia, thereby altering EC function. To begin to address this question and more closely mimic the situation in vivo, we characterized human diabetic EC harvested from insulin-dependent diabetic mothers (IDDM) at the cellular and molecular levels. Human EC were isolated from both normal and IDDM umbilical cords and cellular functions evaluated using standard assays of attachment (% attached cells), proliferation (cpm/cell), resistance to detachment under shear stress (number of cells remaining attached), and glucose uptake (cpm/2 X 10(4) cells). Gene expression of major BM components (collagen type IV, laminin beta 1, and laminin beta 2) was quantified by Northern analysis. Diabetic EC demonstrated increased proliferation (two- to eightfold compared to normals), were 20-40% less resistant to shear stress and took up glucose 10-15% more slowly than normal EC. Furthermore, Northern analysis showed that the expression of major BM components was increased by an average of 10-18% in diabetic cells compared to normal cells. These results were consistent with in vivo observations and previously published data.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Surgery, University of Southern California School of Medicine, Los Angeles 90033.
authors.forename: A
authors.initials: A
authors.lastname: Sank
authors.forename: D
authors.initials: D
authors.lastname: Wei
authors.forename: J
authors.initials: J
authors.lastname: Reid
authors.forename: D
authors.initials: D
authors.lastname: Ertl
authors.forename: M
authors.initials: M
authors.lastname: Nimni
authors.forename: F
authors.initials: F
authors.lastname: Weaver
authors.forename: A
authors.initials: A
authors.lastname: Yellin
authors.forename: T L
authors.initials: TL
authors.lastname: Tuan
mesh_terms: D001485:Basement Membrane / Q000737:chemistry / Q000502:physiology / Q000648:ultrastructure; D015152:Blotting, Northern; D002448:Cell Adhesion / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D003094:Collagen / Q000032:analysis / Q000235:genetics; D004247:DNA / Q000032:analysis / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000737:chemistry / Q000473:pathology* / Q000502:physiology; D005109:Extracellular Matrix / Q000737:chemistry / Q000473:pathology / Q000502:physiology; D005260:Female; D005947:Glucose / Q000493:pharmacokinetics; D006031:Glycosylation; D006801:Humans; D006965:Hyperplasia / Q000473:pathology; D007797:Laminin / Q000032:analysis / Q000235:genetics; D010641:Phenotype; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000473:pathology / Q000503:physiopathology
chemical_list: D007797:Laminin; D003094:Collagen; D004247:DNA; D005947:Glucose