Matrix metalloproteinases in premature coronary atherosclerosis: influence of inhibitors, inflammation, and genetic polymorphisms.
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.
Nanni
Samuele
S
Institute of Cardiology, Policlinico S. Orsola-Malpighi of Bologna, Italy. bibcard@med.unibo.it
Melandri
Giovanni
G
Hanemaaijer
Roeland
R
Cervi
Vittorio
V
Tomasi
Luciana
L
Altimari
Annalisa
A
Van Lent
Natascha
N
Tricoci
Pierluigi
P
Bacchi
Letizia
L
Branzi
Angelo
A
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
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