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Increased Synthesis and Secretion of CRP in EC in Hyperglycemia‐Role of NFKb
Author(s) -
Devaraj Sridevi,
Dasu Mohan R,
Jialal Ishwarlal
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a12
Subject(s) - secretion , inflammation , medicine , endocrinology , downregulation and upregulation , diabetes mellitus , interleukin 6 , c reactive protein , immunology , chemistry , gene , biochemistry
Inflammation is pivotal in atherosclerosis. C‐reactive protein (CRP), a cardiovascular risk marker may promote atherogenesis. A major source of CRP is the liver. We recently showed that human aortic endothelial cells (HAEC) synthesize and secrete CRP. Diabetes is a pro‐inflammatory state, associated with accelerated atherosclerosis. CRP levels are increased in diabetes and predict the onset of diabetes. However, there is no data with regards to the regulation of CRP synthesis and secretion in HAEC, especially under hyperglycemia (HG). In liver cell lines, CRP synthesis is largely under the control of the transcription factors, NFKb, STAT and CEB/P. In this study, HAEC were incubated in presence of mannitol or euglycemic conditions (EG, 5.5mM) or hyperglycemia (HG, 15mM) for 48 hours. HG resulted in significant upregulation of CRPmRNA and secreted CRP. Also, there was a significant increase in NFKb activity in the nuclear extracts along with increases in STAT1 and CEBP beta activities in presence of HG. HG failed to augment CRP expression and secretion in presence of the dominant negative NFKb but not control vector. Thus, while transcription of CRP in liver derived cell lines appears to be CEBP centric, it appears that in HAEC, it may be NFKb centric, since dominant negative NFkb significantly reversed the induction of CRP synthesis and secretion in HAEC. These findings have major implications with regards to controlling inflammation in diabetes