Gender specific associations between matrix metalloproteinases and inflammatory markers in post myocardial infarction patients.
OBJECTIVE
Atherothrombotic disease in the coronary arteries leads to myocardial infarction (MI) through plaque rupture or erosion of the endothelium, the former mechanism predominating in men and the latter in women. Inflammation is a key feature of these processes, and the interplay between inflammation and matrix metalloproteinases (MMPs) in this context is not fully understood. In this study, we investigated the association between inflammatory markers and MMPs in men and women.


METHODS
Blood samples were drawn 3 months after a first MI in 387 patients and 387 sex- and age-matched controls (82% men). C-reactive protein (CRP), interleukin-6 (IL-6), IL-8, -18, tumour necrosis factor-alpha (TNF-alpha), macrophage chemoattractant protein-1 (MCP-1), MMP-1, -3 and -9 were measured. Coronary angiography was performed in 243 of the patients, and they were classified into 0-, 1-, 2- or 3-vessel disease groups.


RESULTS
CRP, IL-6, -8, -18 and TNF-alpha were higher, and MMP-3 and -9 were lower, in patients than in controls. A greater proportion of women (49%) had 0-vessel disease than men (16%, p<0.0001). A gender specific pattern of associations between inflammatory markers and MMPs was found as IL-6 (r(S)=0.29, p<0.05), IL-18 (r(S)=0.34, p<0.01) and MCP-1 (r(S)=0.35, p<0.01) correlated with MMP-3 in female patients, whereas CRP (r(S)=0.23, p<0.0001), IL-6 (r(S)=0.13, p<0.05) and IL-8 (r(S)=-0.21, p<0.01) correlated with MMP-9 in male patients.


CONCLUSIONS
The present study demonstrates different patterns of association between inflammatory markers and MMPs in men and women, strengthening the hypothesis of gender specific differences in pathophysiological mechanisms of MI.
Samnegård
Ann
A
Atherosclerosis Research Unit, Center for Molecular Medicine, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden. ann.samnegard@ki.se
Hulthe
Johannes
J
Silveira
Angela
A
Ericsson
Carl-Göran
CG
Hamsten
Anders
A
Eriksson
Per
P
D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D018932:Chemokine CCL2 / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood / Q000276:immunology; D005260:Female; D006801:Humans; D020382:Interleukin-18 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000097:blood*; D019278:Matrix Metalloproteinase 3 / Q000097:blood*; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D009203:Myocardial Infarction / Q000097:blood* / Q000276:immunology; D012727:Sex Characteristics; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D015415:Biomarkers; C111835:CCL2 protein, human; D018932:Chemokine CCL2; C508600:IL6 protein, human; D020382:Interleukin-18; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein; D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1