title: Effects of atorvastatin, simvastatin, and fenofibrate therapy on monocyte chemoattractant protein-1 secretion in patients with hyperlipidemia.
abstract: OBJECTIVE
  Monocytes that migrate into the arterial wall participate in the development and, eventually, rupture of the atherosclerotic plaque. The aim of this study was to evaluate the secretion of monocyte chemoattractant protein-1 (MCP-1) by monocytes from hyperlipidemic patients treated with hypolipidemic drugs, namely fenofibrate, simvastatin, or atorvastatin to determine what role is played by these drugs in the development and stabilization of the atherosclerotic plaque.
  
  
  METHODS
  Fifty-four hyperlipidemic patients, who did not respond to a low-fat diet, were treated with fenofibrate, simvastatin, or atorvastatin (18 patients in each group) for 1 month. The control group included 18 normolipidemic, healthy, age-matched participants. Ten hyperlipidemic patients were effectively treated with hypolipidemic diet alone for 1 month. This group was compared with a control group of ten healthy subjects. To accurately evaluate the adhesion molecule levels, we excluded hyperlipidemic patients and control subjects with any inflammatory disease. Before and after treatment, monocytes were isolated from peripheral blood. After stimulation with lipopolysaccharide (LPS), MCP-1 secretion was measured by enzyme-linked immunosorbent assay (ELISA).
  
  
  RESULTS
  MCP-1 levels were significantly higher in hyperlipidemic patients than controls: 15.8+/-0.47, 16.7+/-0.23, and 14.9+/-0.45 compared with 12.36+/-0.42 ng/ml. Fenofibrate, atorvastatin, and simvastatin significantly decreased MCP-1 levels from 15.8+/-0.47 to 8.79+/-0.89, from 16.7+/-0.23 to 7.46+/-0.73, and from 14.9+/-0.45 to 10.3+/-0.8 ng/ml, respectively. In the diet-treated group of hyperlipidemic patients, the level of MCP-1 before therapy was significantly higher than in controls (16.89+/-0.31 vs 12.45+/-0.36 ng/ml). The diet therapy caused a significant decrease in levels of MCP-1 to 15.1+/-0.36 ng/ml. There was a correlation between the decreased levels of lipids and the decreased release of MCP-1 in the patients treated with hypolipemic drugs.
  
  
  CONCLUSIONS
  The drug-induced decrease in MCP-1 secretion in hyperlipidemic patients suggests that, apart from acting on lipids, the hypolipidemic drugs studied may directly inhibit the activity of monocytes.
authors.affiliation: Department of Clinical Pharmacology, Medical University of Silesia, 40-752 Katowice, 18 Medyków, Poland. farmklin@infomed.slam.katowice.pl
authors.forename: J
authors.initials: J
authors.lastname: Kowalski
authors.forename: B
authors.initials: B
authors.lastname: Okopień
authors.forename: A
authors.initials: A
authors.lastname: Madej
authors.forename: M
authors.initials: M
authors.lastname: Zieliński
authors.forename: D
authors.initials: D
authors.lastname: Belowski
authors.forename: Z
authors.initials: Z
authors.lastname: Kalina
authors.forename: Z S
authors.initials: ZS
authors.lastname: Herman
mesh_terms: D000069059:Atorvastatin; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000097:blood* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D011345:Fenofibrate / Q000494:pharmacology* / Q000627:therapeutic use; D006538:Heptanoic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D011758:Pyrroles / Q000494:pharmacology* / Q000627:therapeutic use; D019821:Simvastatin / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D018932:Chemokine CCL2; D006538:Heptanoic Acids; D000960:Hypolipidemic Agents; D008055:Lipids; D011758:Pyrroles; D000069059:Atorvastatin; D019821:Simvastatin; D011345:Fenofibrate