Effects of fluvastatin, an HMG-CoA reductase inhibitor, on serum levels of interleukin-18 and matrix metalloproteinase-9 in patients with hypercholesterolemia.
BACKGROUND
Interleukin-18 (IL-18), a novel proinflammatory marker, and matrix metalloproteinase-9 (MMP-9) represent the indices of plaque stability. It is unknown whether hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins), which provide anti-inflammatory and endothelium protection effects, have the property of stabilizing plaque in patients with hypercholesterolemia.


OBJECTIVE
The study was designed to investigate the influence of statin therapy in circulating IL-18, MMP-9, and endothelial function.


METHODS
We investigated the effects of a 12-week therapy with fluvastatin on IL-18, MMP-9, and endothelial function in patients with hypercholesterolemia.


RESULTS
Compared with placebo, fluvastatin significantly improved flow-mediated vasodilatation to hyperemia, a hallmark of endothelial function [from 3.8% (-3.9 approximately 15.2) to 5.9% (-0.3 approximately 13.2), p = 0.001], and attenuated plasma levels of high sensitivity C-reactive protein (hsCRP) [from 1.3 (0.3 approximately 7.7) to 1.1 mg/l (0.2 approximately 3.5), p = 0.018], IL-18 [from 247.6 (145.4 approximately 378.4) to 196.4 pg/dl (90.7 approximately 380.2), p <0.001], total MMP-9 (from 58 +/- 46.3 to 39.4 +/- 22.4 ng/dl, p = 0.023), and MMP-9 activity [from 6.4 (3.6 approximately 27) to 5.6 ng/dl (3.1 approximately 13.7)]. However, no significant correlation was found between the degree of changes in lipid profile and flow-mediated dilatation (FMD) and plasma concentration of IL-18 and MMP-9.


CONCLUSIONS
Fluvastatin reduced plasma concentrations of IL-18 and MMP-9, and improved endothelial function in patients with hypercholesterolemia independent of its lipid-lowering effect.
Leu
Hsin-Bang
HB
National Yang-Ming University, School of Medicine.
Chen
Jaw-Wen
JW
Wu
Tao-Cheng
TC
Ding
Yu-An
YA
Lin
Shing-Jong
SJ
Charng
Min-Ji
MJ
D000368:Aged; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000187:drug effects / Q000378:metabolism; D008078:Cholesterol, LDL / Q000187:drug effects / Q000378:metabolism; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D005229:Fatty Acids, Monounsaturated / Q000627:therapeutic use*; D005260:Female; D000077340:Fluvastatin; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000097:blood* / Q000188:drug therapy; D007211:Indoles / Q000627:therapeutic use*; D020382:Interleukin-18 / Q000097:blood*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood* / Q000187:drug effects; D008875:Middle Aged; D016896:Treatment Outcome; D014664:Vasodilation / Q000187:drug effects
D000924:Anticholesteremic Agents; D015415:Biomarkers; D008078:Cholesterol, LDL; D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D020382:Interleukin-18; D000077340:Fluvastatin; D002097:C-Reactive Protein; D020780:Matrix Metalloproteinase 9