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 language | English (US) |
|---|---|
| Pages (from-to) | 290-300 |
| Number of pages | 11 |
| Journal | Drug Metabolism Letters |
| Volume | 2 |
| Issue number | 4 |
| DOIs | |
| State | Published - 2008 |
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Keywords
- Adiponectin
- Carbon monoxide
- Diabetes
- Inflammation
- Thrombomodulin
- Vascular repair
ASJC Scopus subject areas
- Clinical Biochemistry
- Biochemistry, medical
- Pharmacology (medical)
- Pharmaceutical Science
Cite this
Heme oxygenase-derived carbon monoxide restores vascular function in type 1 diabetes. / Rodella, Luigi F.; Vanella, Luca; Peterson, Stephen J.; Drummond, George; Rezzani, Rita; Falck, John R.; Abraham, Nader G.
In: Drug Metabolism Letters, Vol. 2, No. 4, 2008, p. 290-300.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Heme oxygenase-derived carbon monoxide restores vascular function in type 1 diabetes
AU - Rodella, Luigi F.
AU - Vanella, Luca
AU - Peterson, Stephen J.
AU - Drummond, George
AU - Rezzani, Rita
AU - Falck, John R.
AU - Abraham, Nader G.
PY - 2008
Y1 - 2008
N2 - 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.
AB - 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.
KW - Adiponectin
KW - Carbon monoxide
KW - Diabetes
KW - Inflammation
KW - Thrombomodulin
KW - Vascular repair
UR - http://www.scopus.com/inward/record.url?scp=65249172474&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=65249172474&partnerID=8YFLogxK
U2 - 10.2174/187231208786734058
DO - 10.2174/187231208786734058
M3 - Article
C2 - 19356108
AN - SCOPUS:65249172474
VL - 2
SP - 290
EP - 300
JO - Drug Metabolism Letters
JF - Drug Metabolism Letters
SN - 1872-3128
IS - 4
ER -