title: Impact of Statin Therapy on Plasma MMP-3, MMP-9, and TIMP-1 Concentrations: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials.
abstract: Tissue inhibitors of metalloproteinases (TIMPs) and matrix metalloproteinases (MMPs) are associated with the development of atherosclerosis and cardiovascular disease. Statin therapy has been shown to modulate MMPs and TIMP-1 levels, but clinical findings have not been conclusive. This study aimed to systematically review the clinical findings on the impact of statin therapy on plasma MMP-9, MMP-3, and TIMP-1 levels and calculate an effect size for the mentioned effect through a meta-analysis of available data. A total of 10 eligible studies with 11 treatment arms were included in the meta-analysis. Statin therapy had no significant effect on plasma MMP-9 (standardized mean difference [SMD]: -0.23, 95% confidence interval [CI]: -0.69 to 0.24, P = .345) nor MMP-3 concentrations (SMD: -0.004, 95% CI: -0.60 to 0.59, P = .990). However, meta-analysis demonstrated that statin therapy significantly decreases plasma TIMP-1 levels (SMD: -0.30, 95% CI: -0.56 to -0.03, P = .029). Random-effects meta-regression indicated that neither treatment duration nor changes in low-density lipoprotein cholesterol levels are associated with changes in plasma MMP-9 levels following statin therapy. The results of the present meta-analysis suggested a significant reduction in plasma concentrations of TIMP-1, but not MMP-9 and MMP-3, following statin therapy.
authors.affiliation: 1 Dipartimento di Scienze cliniche Specialistiche ed Odontostomatologiche, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Gianna
authors.initials: G
authors.lastname: Ferretti
authors.affiliation: 2 Dipartimento di Scienze della Vita e dell'Ambiente, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Bacchetti
authors.affiliation: 3 Department of Hypertension, WAM University Hospital in Lodz, Medical University of Łódź, Łódź, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Banach
authors.affiliation: 4 Biomedical Research Unit, Mexican Social Security Institute, Durango, Mexico.
authors.forename: Luis E
authors.initials: LE
authors.lastname: Simental-Mendía
authors.affiliation: 5 Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.|6 Metabolic Research Centre, Royal Perth Hospital, School of Medicine and Pharmacology, University of Western Australia, Perth, Australia.
authors.forename: Amirhossein
authors.initials: A
authors.lastname: Sahebkar
mesh_terms: D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood* / Q000188:drug therapy*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D019278:Matrix Metalloproteinase 3 / Q000097:blood*; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D016032:Randomized Controlled Trials as Topic; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*
chemical_list: D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019715:Tissue Inhibitor of Metalloproteinase-1; D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9
keywords: cardiovascular disease; matrix metalloproteinase; statins; tissue inhibitors of metalloproteinases