title: Serum profiles of matrix metalloproteinases and their tissue inhibitor in patients with acute coronary syndromes. The effects of short-term atorvastatin administration.
abstract: There is increasing evidence that abnormal cytokine expression and increased metalloproteinase activity are implicated in the pathophysiology of acute coronary syndromes. This study investigates the serum profiles of representative metalloproteinases (MMP-1, -2, -9) and their tissue inhibitor (TIMP-1) in patients with myocardial infarction (MI) and unstable angina (UA) in relation to circulating proinflammatory cytokine (TNF-alpha and IL-6) activity. Furthermore, we examined the effects of a 30-day treatment with atorvastatin on serum levels of these inflammatory factors. Serum concentrations of MMP-1, -2, -9, TIMP-1, IL-6 and TNF-alpha were measured (enzyme-linked immunosorbent assay (ELISA) method) in 23 acute myocardial infarction patients and 20 unstable angina patients on 0 day, 1st, 3rd, 7th and 30th day after admission. Sixteen normal volunteers were used as healthy controls. Additionally, 12 patients of myocardial infarction group and 11 patients of unstable angina group were treated with atorvastatin (20 mg/day) for 30 days in a randomized design. In patients with myocardial infarction and unstable angina, serum levels of MMP-2, -9, TIMP-1, TNF-alpha and IL-6 were significantly higher than those of healthy controls in all time frames (p<0.05). In the group of unstable angina patients, we observed a statistically significant reduction in the levels of MMP-9, TIMP-1 and IL-6 after the 30-day atorvastatin administration. Our results suggest that serum MMPs, TIMP-1 and proinflammatory cytokines play an important role in the pathophysiology of the acute coronary syndromes. The reduction of these factors by short-term atorvastatin administration may provide a new insight into the pleiotropic effects of statins on unstable coronary artery disease.
authors.affiliation: Cardiology Department, University of Thrace, Leoforos Dimokratias 116, GR: 68100 Alexandroupolis, Greece. dtziakas@hotmail.com
authors.forename: Dimitrios N
authors.initials: DN
authors.lastname: Tziakas
authors.forename: Georgios K
authors.initials: GK
authors.lastname: Chalikias
authors.forename: John T
authors.initials: JT
authors.lastname: Parissis
authors.forename: Eleni I
authors.initials: EI
authors.lastname: Hatzinikolaou
authors.forename: Elias D
authors.initials: ED
authors.lastname: Papadopoulos
authors.forename: Grigorios A
authors.initials: GA
authors.lastname: Tripsiannis
authors.forename: Evropi G
authors.initials: EG
authors.lastname: Papadopoulou
authors.forename: Ioannis K
authors.initials: IK
authors.lastname: Tentes
authors.forename: Spilios M
authors.initials: SM
authors.lastname: Karas
authors.forename: Dimitrios I
authors.initials: DI
authors.lastname: Chatseras
mesh_terms: D000368:Aged; D000789:Angina, Unstable / Q000097:blood / Q000276:immunology*; D000924:Anticholesteremic Agents / Q000494:pharmacology; D000069059:Atorvastatin; D016207:Cytokines / Q000097:blood / Q000187:drug effects / Q000276:immunology; D005260:Female; D006538:Heptanoic Acids / Q000494:pharmacology; D006801:Humans; D008297:Male; D020782:Matrix Metalloproteinases / Q000097:blood* / Q000187:drug effects / Q000276:immunology; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000276:immunology*; D011758:Pyrroles / Q000494:pharmacology; D019714:Tissue Inhibitor of Metalloproteinases / Q000097:blood* / Q000187:drug effects / Q000276:immunology
chemical_list: D000924:Anticholesteremic Agents; D016207:Cytokines; D006538:Heptanoic Acids; D011758:Pyrroles; D019714:Tissue Inhibitor of Metalloproteinases; D000069059:Atorvastatin; D020782:Matrix Metalloproteinases