Elevated levels of circulating matrix metalloproteinase-9 are associated with a dysregulated cortisol rhythm--A case-control study of coronary artery disease

Abstract

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.