Adiponectin decreases C-reactive protein synthesis and secretion from endothelial cells: evidence for an adipose tissue-vascular loop.
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).


RESULTS
Adiponectin dose-dependently reduced CRP mRNA and protein from HAECs. Adiponectin treatment of HAECs significantly decreased IkappaB phosphorylation and NFkappaB binding activity. There was no effect of adiponectin on STAT or C/EBP transcriptional activity. Adiponectin also activated AMP kinase resulting in decreased NFkappaB 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 NFkappaB. 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.
Devaraj
Sridevi
S
Laboratory for Atherosclerosis and Metabolic Research, 4635 Second Avenue, Sacramento, CA 95817, USA.
Torok
Natalie
N
Dasu
Mohan R
MR
Samols
David
D
Jialal
Ishwarlal
I
D000263:Adenylate Kinase / Q000378:metabolism; D052242:Adiponectin / Q000378:metabolism*; D000818:Animals; D002097:C-Reactive Protein / Q000235:genetics / Q000378:metabolism*; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism; D002478:Cells, Cultured; D015536:Down-Regulation; D042783:Endothelial Cells / Q000201:enzymology / Q000378:metabolism*; D004789:Enzyme Activation; D005947:Glucose / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D050791:STAT Transcription Factors / Q000378:metabolism; D014162:Transfection
D052242:Adiponectin; D022782:CCAAT-Enhancer-Binding Protein-beta; D020672:I-kappa B Proteins; D016328:NF-kappa B; D012333:RNA, Messenger; D050791:STAT Transcription Factors; D002097:C-Reactive Protein; D020928:Mitogen-Activated Protein Kinases; D000263:Adenylate Kinase; D005947:Glucose