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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:1368.)
© 2008 American Heart Association, Inc.

Cell Biology and Signaling

Adiponectin Decreases C-Reactive Protein Synthesis and Secretion From Endothelial Cells

Evidence for an Adipose Tissue-Vascular Loop

Sridevi Devaraj; Natalie Torok; Mohan R. Dasu; David Samols; Ishwarlal Jialal

From the Laboratory for Atherosclerosis and Metabolic Research (S.D., M.R.D., I.J.) and the Department of Internal Medicine (N.T.), UC Davis Medical Center, Sacramento, Calif; and the Department of Biochemistry (D.S.), Case Western Reserve University, Ohio.

Correspondence to Ishwarlal Jialal, MD, PhD, Director, Laboratory for Atherosclerosis and Metabolic Research, Research Bldg I Rm 3000, 4635 Second Avenue, Sacramento, CA 95817. E-mail ijialal{at}ucdavis.edu

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 IB phosphorylation and NFB binding activity. There was no effect of adiponectin on STAT or C/EBP transcriptional activity. Adiponectin also activated AMP kinase resulting in decreased NFB 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 NFB. 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.

We tested whether adiponectin reduces CRP synthesis and secretion in HAECs under normoglycemic (5.5 mmol/L glucose) and hyperglycemic conditions (15 mmol/L glucose). Adiponectin reduced CRP mRNA and protein under hyperglycemic conditions via upregulation of AMP kinase and downregulation of NFêB. Similar findings were observed in rat primary hepatocytes.

Key Words: CRP • adiponectin • endothelium • adipose

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A Novel Role for Adiponectin in the Regulation of Inflammation

Noriyuki Ouchi and Kenneth Walsh
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