title: Matrix metalloproteinases in premature coronary atherosclerosis: influence of inhibitors, inflammation, and genetic polymorphisms.
abstract: Matrix metalloproteinases (MMPs) are thought to participate in the pathogenesis of coronary artery disease (CAD), particularly in the occurrence of acute coronary syndrome (ACS). Little is known about human in vivo MMP regulation in CAD. The expression and regulation of MMPs and their tissue inhibitors (TIMPs) were evaluated in premature CAD. The distribution of MMP-3 5A/6A and MMP-9 C/T promoter polymorphisms and MMP-9 A/G exon-6 polymorphism were investigated in 200 consecutive male premature CAD patients (aged < or = 55 years) and 201 age-matched male blood donors. Plasma concentrations/activities of MMP-2 and MMP-9 were also measured, as were plasma concentrations of MMP-3, TIMP-1, and TIMP-2 in 80 patients (49 with ACSs and 31 with stable CAD) and 40 controls. Inflammation markers were also obtained. MMP genetic polymorphism distributions did not vary between patients and controls and did not seem to influence their respective MMP plasma levels. Patients showed increased MMP-9 and TIMP-1 concentrations and decreased TIMP-2 concentration and MMP-2 total activity (all P < or = 0.002). Overall, TIMP-1 correlated with C-reactive protein (CPR) (r = 0.594, P < 0.001) and haptoglobin (r = 0.276, P = 0.005), whereas MMP-2 activity correlated inversely with haptoglobin (r = -0.195, P = 0.032). Blood glucose correlated positively with TIMP-1 concentration (r = 0.711, P < 0.001) and negatively with MMP-2 activity (r = -0.250, P = 0.006). In conclusion, MMP and TIMP plasma levels in premature CAD are linked to clinical presentation and markers of inflammation and metabolic disorders rather than to genetic polymorphisms.
authors.affiliation: Institute of Cardiology, Policlinico S. Orsola-Malpighi of Bologna, Italy. bibcard@med.unibo.it
authors.forename: Samuele
authors.initials: S
authors.lastname: Nanni
authors.forename: Giovanni
authors.initials: G
authors.lastname: Melandri
authors.forename: Roeland
authors.initials: R
authors.lastname: Hanemaaijer
authors.forename: Vittorio
authors.initials: V
authors.lastname: Cervi
authors.forename: Luciana
authors.initials: L
authors.lastname: Tomasi
authors.forename: Annalisa
authors.initials: A
authors.lastname: Altimari
authors.forename: Natascha
authors.initials: N
authors.lastname: Van Lent
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Tricoci
authors.forename: Letizia
authors.initials: L
authors.lastname: Bacchi
authors.forename: Angelo
authors.initials: A
authors.lastname: Branzi
mesh_terms: D000328:Adult; D002097:C-Reactive Protein / Q000378:metabolism; D003324:Coronary Artery Disease / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology*; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005838:Genotype; D006242:Haptoglobins / Q000378:metabolism; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood; D019278:Matrix Metalloproteinase 3 / Q000097:blood / Q000235:genetics*; D020780:Matrix Metalloproteinase 9 / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000097:blood
chemical_list: D006242:Haptoglobins; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D002097:C-Reactive Protein; D019278:Matrix Metalloproteinase 3; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9