The Effect of C-reactive Protein on Proliferation and VEGF Expression of Human Vascular Smooth Muscle Cells.
- Author:
Duk Hee KANG
1
;
Eun Sun YU
;
Myung Gwan KIM
Author Information
1. Division of Nephrology, Ewha Women's College of Medicine, Seoul, Korea. dhkang@ewha.ac.kr
- Publication Type:Original Article
- Keywords:
CRP;
Atherosclerorsis;
Smooth Muscle Cell;
VEGF;
MAPK
- MeSH:
Atherosclerosis;
Blotting, Western;
C-Reactive Protein*;
Cardiovascular Diseases;
Cell Count;
Cell Proliferation;
Enzyme-Linked Immunosorbent Assay;
Humans*;
Muscle, Smooth, Vascular*;
Myocytes, Smooth Muscle;
p38 Mitogen-Activated Protein Kinases;
Phosphorylation;
Polymerase Chain Reaction;
Protein Kinases;
Renal Insufficiency;
Risk Factors;
RNA, Messenger;
Thymidine;
Vascular Endothelial Growth Factor A*
- From:Korean Journal of Nephrology
2003;22(5):504-511
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
BACKGROUND: Systemic inflammatory reaction (SIR) plays a critical role in the development of cardiovascular disease (CVD). Recent studies have demonstrated that elevated level of C-reactive protein (CRP) is one of the most important risk factor for CVD. CRP is not only a marker of the presence of inflammatory reaction, but also directly participates in the development of endothelial dysfunction and atherosclerosis. Cell proliferation and VEGF expression in vascular smooth muscle wall have been reported as key findings of atherosclerosis. METHODS: To investigate the causal effect of CRP on the development of atherosclerosis, we stimulated human vascular smooth muscle cells (HVSMC) with recombinant human CRP (0.5 to 50 microgram/mL) and examined the effect on cell proliferation (by 3H- thymidine uptake and Cell Counter). VEGF mRNA and protein expression were also evaluated by RT- PCR and ELISA. To investigate the potential intracellular signaling pathway in CRP-induced changes in HVSMC, we assessed the activation of mitogen activated protein kinase (MAPK), p38 and ERK1/2 by CRP by Western blotting. RESULTS: CRP induced a dose- and a time-dependent increase in 3H-thymidine uptake and cell number of HVSMC. CRP also up-regulated the expressions of VEGF mRNA and protein which peaked at 24 hours and 48 hours after exposure, respectively. Stimulation of HVSMC with CRP induced the phosphorylation of MAPK, p38 and ERK1/2 which started at 5 minutes and peaked at 15 minutes after exposure. Pretreament of specific inhibitors of p38 and ERK1/2, SB203580 (10 microM) and PD98010 (50 microM) abolished CRP-induced proliferation and VEGF expression of HVSMCs. CONCLUSION: To the best of our knowledge, this is the first report to show CRP itself induced VEGF expression in HVSMC associated with cell proliferation, which suggested that CRP may actively participate in the development of atherosclerosis via different mechanisms. Clinical implication of these findings with potential therapy targeting "increased CRP itself" need to be carefully evaluated in order to decrease the cardiovascular morbidity and better outcome of renal failure patients.
