Adiponectin Decreases C-Reactive Protein Synthesis and Secretion From Endothelial Cells: Evidence for an Adipose Tissue-Vascular Loop

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 I&kgr;B phosphorylation and NF&kgr;B binding activity. There was no effect of adiponectin on STAT or C/EBP transcriptional activity. Adiponectin also activated AMP kinase resulting in decreased NF&kgr;B 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 NF&kgr;B. 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.

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