| Background Inflammation plays a key role in atherosclerosis and plaque disruption. Monocyte is a critical cell in atherosclerosis and inflmmation. Monocytes are the main resources of the chemokines and metalloproteinase. Monocyte chemoattractant protein-1 (MCP-1) plays a crucial role in monocyte adhesion and migration thus in plaque formation and plaque instability. Matrix metalloproteinase-9 degrades extracellular matrix and weakens the fibrous cap of atherosclerotic plaques, predisposing them to rupture. Some studies suggest that peroxisome proliferator-activated receptor gamma (PPAR Y ) is an important regulator of inflammation of monocytes. Clincal studies show that statin treatment in the early phase of acute coronary syndrome (ACS) reduces recurrent ischemic events. Recent studies also show that statins upregulate PPAR Y expression. However little is know about whether MCP-1 and MMP-9 are increased in patients with ACS and the relationship with the expression of PPAR Y . The relation between statins and upregulation PPAR Y expression and attenuation of inflammation in blood peripheral monocytes from patients with ACS need to be evaluated.Objective The study was designed to examine the effect of atorvastatin on the expression of MCP-1 and PPAR Y and secretions of MCP-1 and MMP-9 in human monocytes in vitro. We also examed plasma levels of MCP-1 and MMP-9 and secretions of MCP-1 and MMP-9 of blood peripheral monocytes(PBM) and the relationship with expression of PPAR Y in patients with ACS. To understand the anti-inlfammatory mechanisms of atorvastatin in early stage of ACS we, observed effects of atorvastatin on levels of MCP-1 and MMP-9 in plasma and in supernate of peripheral blood monocytes from patients with ACS.Methods: PPAR Y and MCP-1 expression of human blood peripheral monocytes incubated with atorvastatin (0.1-10 u mol/L) were analyzed by reverse transcription polymerase chain reaction (RT-PCR). PPAR Y and MCP-1inexpression of peripheral blood monocytes were also analyzed by RT-PCR in 40 patients with ACS and 20 normal control subjects. MCP-1 and MMP-9 levels were measured by enzyme-linked immunosorbent assays (ELISA) in supernate of peripheral blood monocyte incubated with atorvastatin. Levels of MCP-1 and MMP-9 in plasma and in supernate of peripheral blood monocytes were mearsured in 40 patients and 20 normal control subjects by ELISA. In addition, 40 patients with ACS were randomly separated to routine therapy group (n=20) and routine therapy+atorvastatin 10mg/day group, levels of MCP-1 and MMP-9 in plasma and in supernate of peripheral monocytes were measured by ELISA after therapy. Result1. Atorvastatin activated expression of PPAR Y in human monocytes.2. Atorvastatin inhibited expression of MCP-1 and also reduced the Secretions of MCP-1 and MMP-9 up to 73% and 62% respectively (P<0.05) ,in a concentration-dependent manner.3. Plasma levels of MCP-1 and MMP-9 were higher in patients with ACS than in normal control subjects[100(63-170)pg/ml vs 27 ( 17-53 ) pg/ml and 27.9(7.4-48.7) rig/ml vs 11.3 (4.8-29.0) ng/ml respectively (PO.05)].4. Secretions of MCP-1 and MMP-9 in pheripheral blood monocytes were higher in patients with ACS than in control subjects[634(346-863) vs 337 (215-557) pg/ml and 165 (87-215) ng/mlvs84 (53-139) ng/ml (P<0.05)].5. Expression of MCP-1 was significantly increased in patients with ACS while expression of PPAR Y was significantly reduced in patients with ACS compared with control subjects.6. Plasma levels of MCP-1 and MMP-9 were positively correlated with the Secretions of MCPrl and MMP-9 in peripheral blood monocytes respectively (r=0.634 and r=0.580, PO.05). PPARY expression was inversely correlated with plasma MCP-1 and MMP-9 levels(r=-0.408 and r=-0.434 respectively, PO.05).7. MMP-9 and MCP-1 significantly lowered after 4 weeks therapy in two group patients. Compared with routine therapy alone, atorvastatin significantly furtherIVreduced plasma levels of MMP-9 from 26.3(13.9-45.8) to 13(6.5-23.5) ng/ml,MCP...
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