Matrix metalloproteinases in isolated hypercholesterolemia.
OBJECTIVE
Levels of circulating matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are altered in subjects with atherosclerosis. We hypothesized that also otherwise healthy hypercholesterolemic subjects will have altered MMP/TIMP concentrations. To validate this hypothesis, we compared MMPs/TIMPs in patients with moderate isolated hypercholesterolemia before and after atorvastatin therapy and in healthy normolipidemic controls.


METHODS
Twenty-seven otherwise healthy subjects with isolated hypercholesterolemia (total cholesterol 8.3+/-0.3 mmol/L) and 29 healthy normolipidemic controls were included. Patients were treated by atorvastatin for 10 weeks. We studied plasma levels of MMPs (MMP)-2, -3, and -9 and of their TIMPs (TIMP)-1 and -2.


RESULTS
Patients differed from controls by significantly lower MMP-3 [11.6 (5.7-21) vs 18.4 (12-22) ng/mL, P<10-4 (median, range 25-75%)] and TIMP-2 [13.3 (8.8-30.5) vs 22.1 (10.8-39) ng/mL, P=0.02] and by higher TIMP-1 [496 (461-538) vs 483 (456-500) ng/mL, P=0.004]. Atorvastatin decreased significantly TIMP-1 [from 496 (461-538) to 476 (451-525) ng/mL].


CONCLUSIONS
Isolated hypercholesterolemia per se is associated with similar alterations of circulating MMPs and TIMPs as developed symptomatic atherosclerosis. Most consistent link to serum lipids was observed in case of TIMP-1. MMP and TIMP levels probably reflect the atherogenic process in its early stages in these subjects.
Malik
J
J
Third Department of Internal Medicine, General University Hospital and First School of Medicin, Charles University, Prague, Czech Republic. JMALI@LF1.CUNI.CZ
Stulc
T
T
Ceska
R
R
D050197:Atherosclerosis / Q000097:blood; D000069059:Atorvastatin; D005260:Female; D006538:Heptanoic Acids / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000097:blood* / Q000188:drug therapy; D008297:Male; D020782:Matrix Metalloproteinases / Q000097:blood*; D008875:Middle Aged; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood; D019714:Tissue Inhibitor of Metalloproteinases / Q000097:blood
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D019715:Tissue Inhibitor of Metalloproteinase-1; D019714:Tissue Inhibitor of Metalloproteinases; D000069059:Atorvastatin; D020782:Matrix Metalloproteinases