MMP-9 and Its Regulators TIMP-1 and EMMPRIN in Patients with Acute ST-Elevation Myocardial Infarction: A NORDISTEMI Substudy

Abstract

Objectives: The extracellular matrix is involved in wound repair after acute myocardial infarction (AMI). We investigated whether matrix metalloproteinase (MMP)-9, tissue inhibitor of metalloproteinases (TIMP)-1, and the MMP inducer (EMMPRIN) are associated with infarct size, left ventricular function, and clinical outcome in ST-elevation-MI (STEMI). Methods: In 243 STEMI patients, circulating EMMPRIN, MMP-9, and TIMP-1 were analyzed 3 days and 3 months post-AMI. Infarct size and left ventricular ejection fraction were assessed by single-photon emission computed tomography (SPECT) (n = 230/226) and MRI (n = 111/167) at 3 months. Results: EMMPRIN, MMP-9, and TIMP-1 levels and the MMP-9/TIMP-1 ratio declined from day 3 to 3 months (p < 0.001, all). TIMP-1 levels at day 3 correlated significantly with SPECT- and MRI-based infarct size, troponin T (p < 0.04, all), and amino-terminal pro-B-type natriuretic peptide (NT-proBNP; p < 0.001). The upper quartile of day 3 TIMP-1 levels showed an adjusted odds ratio of 5.0 (95% confidence interval 1.2-20.6) for having a large infarct size. An insignificant relationship between MMP-9 and clinical events within 1 year (death, AMI, or stroke) (n = 15) was observed, probably due to the lack of statistical power. Conclusion: The decline in EMMPRIN, MMP-9, and TIMP-1 3 months after acute STEMI is probably due to initial acute-phase processes. The associations between TIMP-1, infarct size, and NT-proBNP indicate a role for TIMP-1 in cardiac remodeling.

Plasma MMP-9 and TIMP-1 levels on ICU admission are associated with 30-day survival

“…Higher circulating MMP-9 and TIMP-1 levels and MMP-9/TIMP-1 ratios were reported in ischemic cardiomyopathy [36] and are associated with disease severity in heart failure [37] and tissue remodeling in myocardial hypertrophy [38]. The TIMP-1 was further shown to correlate with infarct size in ST-elevation myocardial infarction [39]. Both MMP-2 and MMP-9 are involved in several cardiovascular and inflammatory diseases; they have been previously associated with critical disease progression and organ injury; however, their predictive value in a heterogeneous group of critically ill patients has not yet been evaluated.…”

Prediction of the Network Pharmacology‐Based Mechanism for Attenuation of Atherosclerosis in Apolipoprotein E Knockout Mice by Panax notoginseng Saponins

“…Clinical research showed that serum MMP-9 levels could be an early marker of plaque rupture contributing to acute coronary syndrome [25]. e pathological plaque rupture process that involves inflammation and fibrosis in AS could Evidence-Based Complementary and Alternative Medicine be regulated by MMP-9 and TIMP-1 [26]. In the present study, the expression of MMP-9 and TIMP-1 was regulated by PNS, illuminating plaque vulnerability to its products.…”

Left ventricular remodeling and the level of matrix metalloproteinase-9 in patients with coronary artery disease

“…MMP-9 являются желатиназой, которая может деградировать желатины, коллагены и различные компоненты миокарда [14,15]. К тому же MMP-9 способна локализоваться внутри кардиомиоцитов и непосредственно повреждать сократительный аппарат путем расщепления миозина [16,17].…”