High serum matrix metalloproteinase-9 level is associated with diurnal salivary cortisol in patients with acute myocardial infarction - a 3-months follow-up

• Background: Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) are closely associated with inflammation and an increasing body of evidence suggests a role in coronary plaque rupture. We have recently shown that an impaired cortisol secretion is related to the enhanced inflammatory activity in patients with coronary disease. In the present paper, we studied the MMP profile in myocardial infarction (MI), its change over time and relation to diurnal salivary cortisol. Methods: Thirty patients with a first-time MI were assessed at day 1-3, 2 weeks and 3 months. Serum samples were assayed for C-reactive protein (CRP), interleukin-6 (IL-6), MMP-9, MMP-2, MMP-3 and TIMP-1. Free cortisol was measured in a 24-h urine sample and in repeated saliva samples 30 minutes after awakening and in the evening. Results: At 1-3 days, the patients showed increased levels of MMP-9, TIMP-1, IL-6 and CRP and decreased levels of MMP-2 compared to healthy controls. At 2 weeks and 3 months, the MMP-2, IL-6 and CRP levels in patients were similar to controls while the MMP-3 levels increased during follow-up. On the other hand, the levels of MMP-9 and TIMP-1 as well as the MMP-9/TIMP- ratio remained significantly increased in patients from the acute event to 3 months. At all time points, the MI patients showed a flat diurnal cortisol rhythm, as manifested by increased evening cortisol levels. At 2 weeks and 3 months, the evening salivary cortisol was an independent predictor of serum MMP-9 and TIMP-1, but not of MMP-2 or MMP-3. Conclusion: In a 3-months follow-up of patients with acute MI, the serum MMP-9, TIMP-1 and MMP-9/TIMP- 1 ratio remined significantly elevated despite rapid normalizations of MMP-2, IL-6 and CRP. Moreover, MMP-9 and TIMP-1 showed a close association with a flat diurnal cortisol rhythm. The data indicate a link between imbalanced MMP pattern and dysfunctional cortisol response in coronary disease with potential implications for plaque progression.

Keyword

Myocardial infarction

coronary artery disease

cortisol

inflammation

matrix

MEDICINE

MEDICIN

Publication and Content Type

vet (subject category)

ovr (subject category)