Premium
OI‐A‐3
Author(s) -
Zineh I.,
Arant C. B.,
Wessel T. R.,
Schofield R. S.
Publication year - 2006
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2005.12.004
Subject(s) - atorvastatin , dyslipidemia , matrix metalloproteinase , medicine , gastroenterology , endocrinology , disease
BACKGROUND Leukocytes are important in initiation of cardiovascular disease (CVD), in part, through secretion of matrix metalloproteinases (MMPs). Statins may reduce MMP concentrations in hypercholesterolemia. No study has examined the effect of statins on MMP production from leukocytes in patients without overt dyslipidemia. METHODS Normocholesterolemic adults without CVD were eligible if not using lipid‐lowering or anti‐inflammatory medications. After a two‐week run‐in control period, subjects received atorvastatin 80 mg daily. Leukocyte cultures were prepared at baseline and after 4 weeks of therapy from subjects' buffy coat samples. After 24 hours, culture media were collected, and MMP‐8 and MMP‐9 were assayed in duplicate by flow‐based immunofluorescence. Analyses were by paired t‐test with significance set at p<0.05. RESULTS Ten subjects were studied with average age, total cholesterol, LDL, HDL, and triglycerides of 28±10 years, 187±41 mg/dl, 100±36 mg/dl, 65±20 mg/dl, and 109±51 mg/dl, respectively. Atorvastatin reduced MMP‐8 by 38% from 5767 pg/ml to 3548 pg/ml (p=0.02). MMP‐9 was reduced by 9% from 26,636 pg/ml to 24,257 pg/ml (p=0.1). CONCLUSIONS Atorvastatin significantly reduced leukocyte production of MMP‐8 in individuals without dyslipidemia or manifest CVD after four weeks. There was a non‐significant reduction in MMP‐9 concentrations. These data suggest a potential benefit of atorvastatin in individuals without high‐risk for CVD and should be studied further. Clinical Pharmacology & Therapeutics (2005) 79 , P2–P2; doi: 10.1016/j.clpt.2005.12.004