Aortic endothelial cell von Willebrand factor content, and circulating plasminogen activator inhibitor-1 are increased, but expression of endothelial leukocyte adhesion molecules is unchanged in insulin-dependent diabetic BB rats

• Published in: Atherosclerosis Vol. 149; no. 2; pp. 331 - 342
• Main Authors: Ribau, José C.O, Samis, John A, Senis, Yotis A, Maurice, Donald H, Giles, Alan R, DeReske, Marnie, Absher, P.Marlene, Hatton, Mark W.C, Richardson, Mary
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ireland Ltd 01.04.2000; Elsevier
• Subjects: Adhesion molecules; Analysis of Variance; Animals; Aorta, Thoracic - metabolism; Aorta, Thoracic - pathology; BB rats; Biological and medical sciences; Cells, Cultured; Diabetes; Diabetes Mellitus, Type 1 - metabolism; Diabetes Mellitus, Type 1 - pathology; Disease Models, Animal; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Endothelium; Endothelium, Vascular - metabolism; Endothelium, Vascular - pathology; Enzyme-Linked Immunosorbent Assay; Immunohistochemistry; Intercellular Adhesion Molecule-1 - analysis; Male; Medical sciences; PAI-1; Plasminogen Activator Inhibitor 1 - blood; Probability; Rats; Rats, Inbred BB; Reference Values; RNA, Messenger - analysis; Tumors. Hypoglycemia; Vascular Cell Adhesion Molecule-1 - analysis; von Willebrand factor; von Willebrand Factor - analysis; vWF mRNA; vWF mRNA; von Willebrand factor; PAI-1; Adhesion molecules; Diabetes; BB rats; Endothelium; Endocrinopathy; Immunopathology; Endothelial cell; Pathophysiology; Rat; Leukocyte; Pathogenesis; Rodentia; Autoimmune disease; Cardiovascular disease; Gene expression; Plasminogen activator inhibitor 1; Vertebrata; Mammalia; Animal; Insulin dependent diabetes; Aorta; Complication; Adhesin; Willebrand factor
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/S0021-9150(99)00344-5

Endothelial cell injury has been implicated in the increased incidence of vascular disease associated with diabetes mellitus. In diabetic humans, elevated plasma von Willebrand Factor (vWF) has been interpreted as an indication of endothelial damage. In contrast, in an animal model of inherited insulin-dependent diabetes, the bio-breeding (BB) rat, plasma vWF levels did not differ from those in age-matched control rats during the first 7 months of diabetes although morphological evidence of mild aortic endothelial alteration or injury was observed. In the present study efforts have been made to define the endothelial alterations in BB diabetic rats compared to controls more precisely over this time period. Thus, adhesion molecules: intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1(VCAM-1) were evaluated by in situ immunohistochemistry, vWF content was determined by biochemical analysis of aortic extracts and by quantitative immunohistochemistry, plasma vWF levels were measured by ELISA and vWF mRNA by RNAse protection assay. Neither age nor diabetic state significantly affected either the expression of adhesion molecules, or the levels of circulating vWF. Endothelial vWF content was significantly increased in the diabetic vessels, as observed by both approaches but the vWF mRNA content was not different from that in control vessels. Plasma plasminogen activator inhibitor (PAI-1) activity was significantly increased in diabetic animals. In conclusion, endothelial alterations in BB rats associated with diabetes, together with the raised plasma PAI-1 levels, promote the thrombogenic potential of the vessel wall, and are consistent with an increased risk for vascular disease.