Matrix Metalloproteinase 9 as a Predictor of Coronary Atherosclerotic Plaque Instability in Stable Coronary Heart Disease Patients with Elevated Lipoprotein(a) Levels

Abstract

We sought to investigate whether levels of matrix metalloproteinases (MMPs) and their inhibitors predict coronary atherosclerotic plaque instability, as assessed by intravascular ultrasound (IVUS) virtual histology during coronary angiography. Blood samples were collected before angiography in 32 subjects (mean age 56 ± 8 years) with stable coronary heart disease (CHD) and elevated lipoprotein(a) (Lp(a), 94 ± 35 mg/dL). Levels of high-sensitivity C-reactive protein (hsCRP), apolipoprotein B100 (apoB100), MMP-7, MMP-9, tissue inhibitor of metalloproteinases (TIMP)-1, and TIMP-2 were determined using commercially available enzyme-linked immunosorbent assay kits. Results. The morphology of a total of sixty coronary lesions was assessed by virtual histology IVUS imaging. Eleven (18%) plaques in nine (28%) patients were classified as plaques with an unstable phenotype or a thin-cap fibroatheroma. Age, low-density lipoprotein cholesterol, apoB100, MMP-7, and MMP-9 levels were positively associated with necrotic core volume. Conversely, there was a negative relationship between MMP-7 and -9 levels and fibrous and fibro-fatty tissue volume. Multivariate regression analysis revealed that MMP-9 is a strong independent predictor of atherosclerotic plaque instability in stable CHD patients. In stable CHD patients with elevated Lp(a), MMP-9 levels are positively associated with the size of the necrotic core of coronary atherosclerotic plaques.

The Role of Matrix Metalloproteinase-9 in Atherosclerotic Plaque Instability

“…Inflammatory cells can release large amounts of MMP-9 into plaque tissue, which can then degrade the ECM, resulting in a thin fibrous cap and plaque instability. Numerous studies have demonstrated that MMP-9 levels are higher in vulnerable plaques than in stable plaques, and high circulating levels of MMP-9 are closely related to adverse cardiovascular and cerebrovascular events [ 48 , 53 , 62 , 141 – 143 ]. Depletion of the MMP-9 gene or inhibition of MMP-9 expression or activity can significantly prevent plaque instability.…”

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

“…In the early phase of myocardial infarction, MMP‑9 release is stimulated, as it cleaves mediators derived from neutrophils and dying cardiomyocytes [ 21 ]. The MMP‑9 plasma levels are elevated in coronary heart disease [ 26 , 27 ] and associated with atherosclerotic plaque destabilization [ 28 , 29 ], acute coronary events [ 30 , 31 ] and mortality [ 32 ] in these patients. Accordingly, MMP‑9 was shown to be up-regulated during heart failure [ 33 ].…”

Characterization of Matrix Metalloprotease-9 Gene from Nile tilapia (Oreochromis niloticus) and Its High-Level Expression Induced by the Streptococcus agalactiae Challenge

“…MMP-9 is also the most upregulated gene following the Listeria infection in zebrafish, and can be used a protective molecule [12]. Besides, MMP-9 is a strong, independent predictor of atherosclerotic plaque instability [45]. The results suggest that NtMMP-9 (aNtMMP-9) may have a basic function to regulate inflammatory and immune responses of tilapia against a S. agalactiae infection.…”