Interferon-gamma increases the ratio of matrix metalloproteinase-9/tissue inhibitor of metalloproteinase-1 in peripheral monocytes from patients with coronary artery disease.
Acute coronary syndromes (ACS) may be triggered by acute infections. Systemic production of interferon gamma (IFN-γ) is induced during infection and regulates the production of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs), both important in plaque stability. This study evaluates the effect of IFN-γ on the MMPs/TIMP-1 ratio in cultured monocytes from 30 patients with stable coronary artery disease (CAD), 30 with unstable angina (UA) or non-ST-segment elevation myocardial infarction (NSTEMI), and 30 healthy blood donors. Supernatant concentrations of MMP-1, -2, -9, and TIMP-1 were measured by enzyme-linked immunoassays. Basal concentration of MMP-1 and TIMP-1 was similar between groups, while MMP-2 was higher in healthy individuals and MMP-9 in patients with UA/NSTEMI. Upon IFN-γ stimulation, MMP-9 secretion increased in all groups, while TIMP-1 decreased only in patients with CAD, which in turn result in a strikingly elevation in their mean MMP-9/TIMP-1 ratio. MMP-1/TIMP-1 and MMP-2/TIMP-1 ratios were <1.0 in basal conditions and after stimulation in all groups. Our results suggest that nonstimulated monocytes from patients with stable CAD show a similar behavior than those from healthy individuals. However, stimulation with IFN-γ induces an increase on the MMP-9/TIMP-1 ratio as high as that found in patients with ACS. Thus, it may bring biological plausibility to the association between acute infections and the development of ACS.
Department of Immunology, Instituto Nacional de Cardiología Ignacio, Chávez, Mexico City, Mexico.
Rashidi
R
Springall
Luis M
LM
Amezcua-Guerra
Hector
H
Gonzalez-Pacheco
Janette
J
Furuzawa-Carballeda
Lorena
L
Gomez-Garcia
Ricardo
R
Marquez-Velasco
Ana María
AM
Mejía-Domínguez
Jorge
J
Cossío-Aranda
Carlos
C
Martínez-Sánchez
Rafael
R
Bojalil
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003324:Coronary Artery Disease / Q000175:diagnosis / Q000378:metabolism*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism*
D019715:Tissue Inhibitor of Metalloproteinase-1; D007371:Interferon-gamma; D020780:Matrix Metalloproteinase 9