Capillary and aortic endothelia interact in situ with nonenzymatically glycated albumin and develop specific alterations in early experimental diabetes

D. Popov, M. Hasu, G. Costache, David Stern, M. Simionescu

Research output: Contribution to journalArticle

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Abstract

Diabetic mice (6 weeks duration) were studied to assess the interaction of advanced glycation endproduct-modifed albumin (AGE-Alb) with micro- and macrovascular endothelium, and to evaluate the alterations induced in the ultrastructure of the lung, kidney, and aorta. [125I]-AGE-Alb and AGE-Alb-Au were perfused in situ in the vasculature; the total uptake was quantitated by spectrometry, and the endothelial pathways of AGE-Alb-Au and the morphological alterations of the vascular beds were examined by electron microscopy. The results showed that [125I]-AGE-Alb (0.567 μM) was taken up specifically and saturably by all organs studied, and particularly by the lung. AGE-Alb-Au endocytosis and transcytosis occurred in the pulmonary and aortic endothelia, and were enhanced in diabetic animals. Also in diabetic animals, AGE-Alb-Au was detected throughout the kidney glomerular basement membrane (GBM) and within open filtration slits of podocytes, suggesting altered barrier function. The structural modifications progressed, and at the end of the experimental period, in the lung ~28% of the capillaries and ~25% of the alveoli became compressed or even collapsed, due to the hyperplasia of extracellular matrix and interstitial connective tissue. The presence of adherent intravascular macrophages suggests the development of an inflammatory immune process. The structural modifications observed in kidney glomeruli included thickening (~30%) of the GBM and the disappearance of diaphragms between the cellular processes of podocytes. The aortic endothelium displayed luminal foldings, increased number (2.8-fold) of Weibel-Palade bodies, and proliferation of basal lamina. Together, the results show that in diabetes there is enhanced vascular uptake of AGE-Alb and significant pathomorphological changes of micro- and macrovessels.

Original languageEnglish (US)
Pages (from-to)285-293
Number of pages9
JournalActa Diabetologica
Volume34
Issue number4
DOIs
StatePublished - Jan 1 1997

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Vascular Endothelium
Albumins
Endothelium
Podocytes
Lung
Glomerular Basement Membrane
Blood Vessels
Weibel-Palade Bodies
Kidney Glomerulus
Kidney
Transcytosis
glycosylated serum albumin
Endocytosis
Microvessels
Diaphragm
Basement Membrane
Connective Tissue
Hyperplasia
Extracellular Matrix
Aorta

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Capillary and aortic endothelia interact in situ with nonenzymatically glycated albumin and develop specific alterations in early experimental diabetes. / Popov, D.; Hasu, M.; Costache, G.; Stern, David; Simionescu, M.

In: Acta Diabetologica, Vol. 34, No. 4, 01.01.1997, p. 285-293.

Research output: Contribution to journalArticle

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