Elevated levels of circulating matrix metalloproteinase-9 are associated with a dysregulated cortisol rhythm--A case-control study of coronary artery disease.
A dysregulated cortisol pattern has been found to be associated with systemic inflammatory activity in patients with coronary artery disease (CAD). Matrix metalloproteinase (MMP)-9 is involved in both inflammation and matrix degradation and considered a main contributor to coronary plaque rupture. In this study, we hypothesized that a dysfunctional cortisol response also involved a failure to regulate systemic MMP-9 levels in CAD patients. Total MMP-9, active MMP-9 and the endogenous inhibitor TIMP-1 were measured in 30 CAD patients and 30 healthy controls. Morning and evening cortisol was measured in repeated saliva samples. Patients had higher levels of total and active MMP-9 (both p<0.01) and increased 24-h cortisol output (p<0.05) characterized by higher levels of evening cortisol (p=0.011). MMP-9 was associated with evening cortisol (p<0.001) independent of smoking and inflammatory markers. Compared with controls, patients also showed a blunted cortisol response to stress. After stress, the levels of MMP-9 became significantly reduced in controls whereas they remained unchanged in patients. The data indicate that MMP-9 is differently regulated in patients due to a dysfunctional hypothalamic-pituitary-adrenal (HPA) axis and emphasize the role of MMP-9 as a possible link between stress and cardiovascular disease.
Szymanowski
A
A
Division of Cardiovascular Medicine, Department of Medical and Health Sciences, Linköping University, SE-581 85, Linköping, Sweden.
Nijm
J
J
Kristenson
M
M
Jonasson
L
L
D000368:Aged; D016022:Case-Control Studies; D002940:Circadian Rhythm / Q000502:physiology*; D003324:Coronary Artery Disease / Q000097:blood* / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D016207:Cytokines / Q000032:analysis / Q000097:blood; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000032:analysis / Q000378:metabolism*; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism / Q000502:physiology; D007249:Inflammation / Q000097:blood / Q000150:complications / Q000503:physiopathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood* / Q000502:physiology; D008875:Middle Aged; D010913:Pituitary-Adrenal System / Q000378:metabolism / Q000502:physiology; D012463:Saliva / Q000737:chemistry / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis / Q000097:blood; D015854:Up-Regulation
D016207:Cytokines; D019715:Tissue Inhibitor of Metalloproteinase-1; D020780:Matrix Metalloproteinase 9; D006854:Hydrocortisone