Abstract
Background and Objective - Inflammation is pivotal in atherosclerosis. C-reactive protein (CRP), in addition to being a cardiovascular risk marker, may also be proatherogenic. We have previously shown that in addition to the liver, human aortic endothelial cells (HAECs) synthesize and secrete CRP. Whereas CRP levels are increased in obesity, metabolic syndrome, and diabetes, levels of adiponectin are reduced in these conditions. We tested the hypothesis that adiponectin reduces CRP synthesis and secretion in HAECs under normoglycemic (5.5 mmol/L glucose) and hyperglycemic conditions (15 mmol/L glucose). Methods and Results - Adiponectin dose-dependently reduced CRP mRNA and protein from HAECs. Adiponectin treatment of HAECs significantly decreased IκB phosphorylation and NFκB binding activity. There was no effect of adiponectin on STAT or C/EBP transcriptional activity. Adiponectin also activated AMP kinase resulting in decreased NFκB activity and decreased CRP mRNA and protein. These effects of adiponectin were mimicked by AICAR, an activator of AMPK, and reversed by inhibition of AMPK. Thus, adiponectin reduces CRP synthesis and secretion from HAECs under hyperglycemia via upregulation of AMP kinase and downregulation of NFκB. Similar findings were observed in rat primary hepatocytes. Conclusions - Thus, in obesity and diabetes, the hypoadiponectinemia could exacerbate the proinflammatory state by inducing CRP production.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1368-1374 |
| Number of pages | 7 |
| Journal | Arteriosclerosis, Thrombosis, and Vascular Biology |
| Volume | 28 |
| Issue number | 7 |
| DOIs | |
| State | Published - Jul 1 2008 |
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Keywords
- Adiponectin
- Adipose
- CRP
- Endothelium
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
Cite this
Adiponectin decreases C-reactive protein synthesis and secretion from endothelial cells : Evidence for an adipose tissue-vascular loop. / Devaraj, Sridevi; Torok, Natalia J; Dasu, Mohan R.; Samols, David; Jialal, Ishwarlal.
In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 28, No. 7, 01.07.2008, p. 1368-1374.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Adiponectin decreases C-reactive protein synthesis and secretion from endothelial cells
T2 - Evidence for an adipose tissue-vascular loop
AU - Devaraj, Sridevi
AU - Torok, Natalia J
AU - Dasu, Mohan R.
AU - Samols, David
AU - Jialal, Ishwarlal
PY - 2008/7/1
Y1 - 2008/7/1
N2 - Background and Objective - Inflammation is pivotal in atherosclerosis. C-reactive protein (CRP), in addition to being a cardiovascular risk marker, may also be proatherogenic. We have previously shown that in addition to the liver, human aortic endothelial cells (HAECs) synthesize and secrete CRP. Whereas CRP levels are increased in obesity, metabolic syndrome, and diabetes, levels of adiponectin are reduced in these conditions. We tested the hypothesis that adiponectin reduces CRP synthesis and secretion in HAECs under normoglycemic (5.5 mmol/L glucose) and hyperglycemic conditions (15 mmol/L glucose). Methods and Results - Adiponectin dose-dependently reduced CRP mRNA and protein from HAECs. Adiponectin treatment of HAECs significantly decreased IκB phosphorylation and NFκB binding activity. There was no effect of adiponectin on STAT or C/EBP transcriptional activity. Adiponectin also activated AMP kinase resulting in decreased NFκB activity and decreased CRP mRNA and protein. These effects of adiponectin were mimicked by AICAR, an activator of AMPK, and reversed by inhibition of AMPK. Thus, adiponectin reduces CRP synthesis and secretion from HAECs under hyperglycemia via upregulation of AMP kinase and downregulation of NFκB. Similar findings were observed in rat primary hepatocytes. Conclusions - Thus, in obesity and diabetes, the hypoadiponectinemia could exacerbate the proinflammatory state by inducing CRP production.
AB - Background and Objective - Inflammation is pivotal in atherosclerosis. C-reactive protein (CRP), in addition to being a cardiovascular risk marker, may also be proatherogenic. We have previously shown that in addition to the liver, human aortic endothelial cells (HAECs) synthesize and secrete CRP. Whereas CRP levels are increased in obesity, metabolic syndrome, and diabetes, levels of adiponectin are reduced in these conditions. We tested the hypothesis that adiponectin reduces CRP synthesis and secretion in HAECs under normoglycemic (5.5 mmol/L glucose) and hyperglycemic conditions (15 mmol/L glucose). Methods and Results - Adiponectin dose-dependently reduced CRP mRNA and protein from HAECs. Adiponectin treatment of HAECs significantly decreased IκB phosphorylation and NFκB binding activity. There was no effect of adiponectin on STAT or C/EBP transcriptional activity. Adiponectin also activated AMP kinase resulting in decreased NFκB activity and decreased CRP mRNA and protein. These effects of adiponectin were mimicked by AICAR, an activator of AMPK, and reversed by inhibition of AMPK. Thus, adiponectin reduces CRP synthesis and secretion from HAECs under hyperglycemia via upregulation of AMP kinase and downregulation of NFκB. Similar findings were observed in rat primary hepatocytes. Conclusions - Thus, in obesity and diabetes, the hypoadiponectinemia could exacerbate the proinflammatory state by inducing CRP production.
KW - Adiponectin
KW - Adipose
KW - CRP
KW - Endothelium
UR - http://www.scopus.com/inward/record.url?scp=46249092855&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=46249092855&partnerID=8YFLogxK
U2 - 10.1161/ATVBAHA.108.163303
DO - 10.1161/ATVBAHA.108.163303
M3 - Article
C2 - 18451326
AN - SCOPUS:46249092855
VL - 28
SP - 1368
EP - 1374
JO - Arteriosclerosis, Thrombosis, and Vascular Biology
JF - Arteriosclerosis, Thrombosis, and Vascular Biology
SN - 1079-5642
IS - 7
ER -