Long-term exposure to high glucose up-regulates VCAM-induced endothelial cell adhesiveness to PBMC

C. Esposito, G. Fasoli, A. Plati, N. Bellotti, M. M. Conte, F. Cornacchia, A. Foschi, T. Mazzullo, L. Semeraro, A. Dal Canton

Research output: Contribution to journalArticle

Abstract

Background. The changes induced on endothelial cells by a long-term exposure to high glucose, a situation that mimics the hyperglycemia of diabetics, have not yet been determined. We compared short- and long-term effects of elevated glucose on macrovascular and microvascular endothelial cells. Methods. Endothelial cells were grown in high-glucose media for 24 hours and for 8 weeks. Cell proliferation was evaluated by cell counting, apoptosis and expression of adhesion molecules by flow cytometry; nitric oxide (NO) by measuring the concentration of nitrite/nitrate in the cell supernatant; α2(IV) collagen mRNA and protein by reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. The adhesion of peripheral blood mononuclear cells (PBMCs) to endothelial cells was evaluated by adhesion assay. In some experiments, endothelial cells were preincubated with anti-vascular cell adhesion molecule-1 (VCAM-1) and anti-receptor for advanced glycation end product (RAGE) blocking antibodies. Results. At 24 hours, but not at 8 weeks, high glucose increased endothelial cell proliferation and apoptosis. High glucose did not modify NO synthesis at 24 hours and 8 weeks. Collagen production and expression were increased only after eight weeks. VCAM-1 but not intercellular adhesion molecule-1 was up-regulated after 8 weeks, a change not observed after 24 hours. The adhesion of PBMCs was significantly increased at eight weeks and was completely abrogated by anti-VCAM-1 and by anti-RAGE antibodies. After 24 hours, there was a modest increase of PBMC adhesion that was not blunted by anti-RAGE antibodies. Conclusions. Increased adhesion of PBMCs, caused by up-regulation of VCAM-1 with a mechanism involving advanced glycation end product (AGE) adducts, and augmented collagen deposition are critical effects of long-term high glucose on endothelial cells, and may eventually promote the atherosclerotic process.

Original languageEnglish
Pages (from-to)1842-1849
Number of pages8
JournalKidney International
Volume59
Issue number5
DOIs
Publication statusPublished - 2001

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Keywords

  • Adhesion molecules
  • Atherosclerosis
  • Blood-glucose control
  • Cell proliferation
  • Diabetes
  • Hyperglycemia
  • Vascular disease

ASJC Scopus subject areas

  • Nephrology

Cite this

Esposito, C., Fasoli, G., Plati, A., Bellotti, N., Conte, M. M., Cornacchia, F., Foschi, A., Mazzullo, T., Semeraro, L., & Dal Canton, A. (2001). Long-term exposure to high glucose up-regulates VCAM-induced endothelial cell adhesiveness to PBMC. Kidney International, 59(5), 1842-1849. https://doi.org/10.1046/j.1523-1755.2001.0590051842.x