Heme oxygenase-derived carbon monoxide restores vascular function in type 1 diabetes

Luigi F. Rodella, Luca Vanella, Stephen J. Peterson, George Drummond, Rita Rezzani, John R. Falck, Nader G. Abraham

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Increased heme oxygenase-1 (HO-1) expression improves vascular function by decreasing superoxide and increasing antioxidant levels. We therefore examined if HO-1 induction increased serum adiponectin levels and ameliorated vascular dysfunction in Type 1 diabetes. Administration of either carbon monoxide (CORM-3) or the HO-1 inducers, Resveratrol, and cobalt protoporphyrin (CoPP), increased serum levels of adiponectin (high molecular weight) in diabetic (streptozotocin; STZ-induced) Sprague Dawley rats. Resveratrol and CoPP administration increased HO-1 protein expression and HO activity in the aorta and significantly (p<0.05) increased serum adiponectin levels, compared to untreated diabetic rats. The results obtained with the CO releasing molecule, CORM-3, indicate a direct involvement of CO leading to increased levels of adiponectin. The increase in adiponectin was associated with a significant decrease in circulating endothelial cells (CEC) (p<0.002), decreased EC fragmentations and a significant increase in thrombomodulin (TM) and CD31+ cells (p<0.05). Increased adiponectin levels were associated with a decrease in TNF-α-induced ICAM-1 and VCAM-1 and caspase 3 activity in endothelial cells while phosphorylation of eNOS at Ser-1179 increased. The adiponectin mediated increase in peNOS and pAKT was prevented by the phosphatidylinositol-3 kinase inhibitor, LY294002. In conclusion, there appears to be a temporal HO-1-adiponectin relationship that has a key role in vascular protection in Type 1 diabetes via a mechanism that involves increased levels of carbon monoxide.

Original languageEnglish (US)
Pages (from-to)290-300
Number of pages11
JournalDrug Metabolism Letters
Volume2
Issue number4
DOIs
StatePublished - Dec 1 2008

Keywords

  • Adiponectin
  • Carbon monoxide
  • Diabetes
  • Inflammation
  • Thrombomodulin
  • Vascular repair

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Clinical Biochemistry
  • Biochemistry, medical
  • Pharmacology (medical)

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    Rodella, L. F., Vanella, L., Peterson, S. J., Drummond, G., Rezzani, R., Falck, J. R., & Abraham, N. G. (2008). Heme oxygenase-derived carbon monoxide restores vascular function in type 1 diabetes. Drug Metabolism Letters, 2(4), 290-300. https://doi.org/10.2174/187231208786734058