Effect of C-reactive protein on gene expression in vascular endothelial cells.
C-reactive protein (CRP) is significantly associated with the risk of ischemic cardiovascular disease in epidemiological studies. To explore if CRP has a functional role, we investigated its effect on the gene expression profile of vascular endothelial cells. Human vascular endothelial cells (human umbilical vein endothelial cells and human aortic endothelial cells) were incubated with CRP at various concentrations (0-10 mug/ml). Microarray analysis showed that a total of 11 genes increased (IL-8, core promoter element binding protein, activin A, monocyte chemoattractant protein 1, Exostoses 1, Cbp/p300-interacting transactivator with Glu/Asp-rich COOH-terminal domain 2, plasminogen activator inhibitor 1, fibronectin-1, gravin, connexin43, and sortilin-related receptor-1) and 6 genes decreased (methionine adenosyltransferase 2A, tryptophan-rich basic protein, reticulocalbin 1, membrane-associated RING-CH protein VI, cytoplasmic dynein1, and annexin A(1)) by more than twofold for their mRNA levels. IL-8 was the most significantly upregulated gene (13.6-fold), which demonstrated a clear dose- and time-dependent pattern revealed by quantitative real-time PCR. Cell adhesion assay showed that CRP enhanced the monocyte adhesion to endothelial cell monolayer by 2-fold (P < 0.01), which was partially blocked by an anti-IL-8 antibody (34.2% inhibition, P < 0.01). Inhibition of ERK MAPK pathway using U0126 prevented CRP-induced IL-8 upregulation, and Western blot analysis revealed a rapid activation of ERK1/2 after CRP stimulation. These data showed that CRP can significantly influence gene expressions in vascular endothelium. The CRP-responsive genes suggested that CRP may have a broad functional role in cell growth and differentiation, vascular remodeling and solid tumor development.
Wang
Qingwei
Q
Cardiovascular Research Institute, RW216, Morehouse School of Medicine, 720 Westview Drive SW, Atlanta, GA 30310, USA.
Zhu
Xiaojun
X
Xu
Qin
Q
Ding
Xia
X
Chen
Yuqing E
YE
Song
Qing
Q
D001011:Aorta / Q000166:cytology; D002097:C-Reactive Protein / Q000494:pharmacology* / Q000502:physiology*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D014158:Transcription, Genetic / Q000187:drug effects; D014471:Umbilical Veins / Q000166:cytology
D016209:Interleukin-8; D002097:C-Reactive Protein; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3