Effects of fenofibrate and simvastatin on plasma sICAM-1 and MCP-1 concentrations in patients with hyperlipoproteinemia.
OBJECTIVE
The most important mechanism through which high plasma lipid levels trigger the formation of atherosclerotic lesions involves a change in the expression of adhesion molecules on endothelial and smooth muscle cells. The aim of this study was to evaluate an extralipid effect of fenofibrate and simvastatin by examination of MCP-1 and ICAM-1 plasma concentration after 1-month hypolipemic therapy as well as MCP-1 and ICAM-1 plasma concentration after 1-month therapy with low-fat diet alone.


METHODS
Twenty patients with HLPIIb or HLPIIa, who did not respond to a low-fat diet, were treated with micronized fenofibrate or simvastatin, respectively, for 1 month. The control group included 18 normo-lipidemic, healthy age-matched participants; 10 patients with HLPIIa were effectively treated with a low-fat diet for 1 month. This group was compared to a control group of 10 healthy subjects. The plasma adhesion molecule levels were measured by an ELISA method before and after the treatment. To accurately evaluate the adhesion molecule levels, we excluded hyperlipidemic patients and control subjects with any inflammatory disease.


RESULTS
sICAM-1 levels were significantly higher in HLPIIa and HLPIIb patients (331 +/- 19 ng/ml and 423 +/- 23 ng/ml, respectively) compared with the control group (236 +/- 12 mg/ml). MCP-1 levels were also significantly higher in HLPIIa and HLPIIb patients (170 +/- 9 pg/ml and 183 +/- 15 pg/ml, respectively) compared with the control group (100 +/- 4 pg/ml). Fenofibrate (200 mg daily) significantly decreased sICAM-1 (by 17%) and MCP-1 levels (by 12.5%). Simvastatin (20 mg daily) caused a significant decrease (by 10.5%) in sICAM-1 levels only. Restriction in dietary lipids resulted in a significant decrease in the levels of cholesterol (8%), LDL cholesterol (14.9%) and ApoB (12.7%), which was accompanied by a significant decrease in the levels of sICAM-1 (8.7%) and MCP-1 (16.1%).


CONCLUSIONS
The results of this study suggest that high lipid levels are accompanied by increased levels of sICAM-1 and MCP-1 and that hypolipidemic therapy only slightly decreases the levels of these molecules compared with plasma lipids. The hypolipidemic diet-related decrease in the levels of lipids, ICAM-1 and MCP-1 suggests that it is a drug-induced decrease in lipid levels but not a direct action of the drugs on endothelial cells, smooth muscle cells or macrophages that leads to a decrease in the levels of adhesion molecules.
Kowalski
J
J
Department of Clinical Pharmacology, Medical University of Silesia, Katowice, Medyków, Poland. farmklin@infomed.slam.katowice.pl
Okopien
B
B
Madej
A
A
Zielinski
M
M
Belowski
D
D
Kalina
Z
Z
Herman
Z S
ZS
D018932:Chemokine CCL2 / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D011345:Fenofibrate / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000178:diet therapy / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood*; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D019821:Simvastatin / Q000008:administration & dosage / Q000627:therapeutic use
D018932:Chemokine CCL2; D000960:Hypolipidemic Agents; D008055:Lipids; D018799:Intercellular Adhesion Molecule-1; D019821:Simvastatin; D011345:Fenofibrate