May 29, 2001Circulation832 citationsOpen Access
Modulation of C-Reactive Protein–Mediated Monocyte Chemoattractant Protein-1 Induction in Human Endothelial Cells by Anti-Atherosclerosis Drugs
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Key Result
CRP induced a 7-fold increase in MCP-1 secretion in human endothelial cells, an effect that was significantly inhibited by simvastatin and fenofibrate but not by aspirin.
Key Points
- This research aims to investigate the effects of C-reactive protein on chemokine production in endothelial cells and the modulation by anti-atherosclerosis medications.
- Cultured human umbilical vein endothelial cells were treated with varying concentrations of recombinant human CRP.
- Chemokine secretion was measured using ELISA to quantify MCP-1 and RANTES levels.
- The influence of anti-atherosclerosis drugs, including aspirin, simvastatin, fenofibrate, and ciglitazone, on MCP-1 induction was assessed.
- At 100 microgram/mL CRP, MCP-1 secretion increased 7-fold (baseline < 100 pg/mL), p<0.001.
- Simvastatin (5 micromol/L) significantly inhibited MCP-1 induction compared to control, p<0.005.
- Fenofibrate (100 micromol/L) almost completely abolished MCP-1 induction, while ciglitazone had a moderate effect.
Structured PICO
Do anti-atherosclerosis drugs modulate CRP-induced MCP-1 secretion in human endothelial cells?
P
Population
Cultured human umbilical vein endothelial cells
I
Intervention
Recombinant human CRP (5-100 microgram/mL) with or without anti-atherosclerosis drugs (aspirin, simvastatin, fenofibrate, Wy-14649, ciglitazone)
C
Comparator
Control (no CRP) or CRP alone
O
Outcome
Secretion of chemokines MCP-1 and RANTESsurrogate
Simvastatin and fenofibrate inhibit CRP-induced MCP-1 secretion in human endothelial cells, suggesting a novel anti-inflammatory mechanism for these drugs.
Abstract
BACKGROUND: C-reactive protein (CRP) induces adhesion molecule expression by endothelial cells. However, the effects of CRP on chemokine expression by endothelial cells are not known. METHODS AND RESULTS: We tested the effects of CRP on the production of the chemokines monocyte chemoattractant protein-1 (MCP-1) and RANTES in cultured human umbilical vein endothelial cells. The secretion of chemokines was assessed by ELISA. Incubation with 100 microgram/mL recombinant human CRP induced a 7-fold increase in MCP-1 but no change in RANTES secretion. We showed that the effect of CRP on MCP-1 was present even at 5 microgram/mL CRP, with stepwise increases as the CRP concentration was increased to 10, 50, and 100 microgram/mL. The effect of CRP on MCP-1 induction was not influenced by aspirin (at concentrations up to 1 mmol/L), but it was significantly inhibited by 5 micromol/L simvastatin. The peroxisome proliferator-activated receptor-alpha activators fenofibrate (100 micromol/L) and Wy-14649 (100 micromol/L) almost completely abolished the induction of MCP-1, but the peroxisome proliferator-activated receptor-gamma activator ciglitazone had only a moderate effect. CONCLUSIONS: These results further strengthen the role of CRP in the pathogenesis of vascular inflammation and, likely, atherosclerosis and provide a crucial insight into a novel mechanism of action of anti-atherosclerosis drugs such as simvastatin and fenofibrate.
Cite This Study
Pasceri et al. (2001) studied Vascular inflammation. C-reactive protein and anti-atherosclerosis drugs was evaluated on Secretion of chemokines MCP-1 and RANTES. CRP induced a 7-fold increase in MCP-1 secretion in human endothelial cells, an effect that was significantly inhibited by simvastatin and fenofibrate but not by aspirin.