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

Marat Ezhov,Maya Safarova,Sergei Pokrovsky,Maksim Mitroshkin,Yuri Matchin,Olga Afanasieva

doi:10.3390/biom9040129

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.

Highlights

Morphologic findings indicate that atheroma composition is not related to the degree of stenosis of the coronary artery, and about 40% of atherosclerotic plaques in patients with stable angina have a pool of extracellular lipids [1]
This study provides evidence that elevated levels of matrix metalloproteinases (MMPs)-7, MMP-9, and apolipoprotein B100 (apoB100) are directly associated with the size of the necrotic core of the coronary atherosclerotic plaque, as assessed by VHIVUS in patients with stable coronary heart disease (CHD) and elevated Lp(a)
We suggest that high levels of MMP-9 can be utilized as a marker of coronary plaque vulnerability

Summary

Introduction

Morphologic findings indicate that atheroma composition is not related to the degree of stenosis of the coronary artery, and about 40% of atherosclerotic plaques in patients with stable angina have a pool of extracellular lipids [1]. Precursors of plaque destabilization and evolution into a plaque at a high risk of rupture in the milieu of stable coronary artery disease (CAD) remain unclear. The phenotype of an unstable atheroma includes a thin fibrous cap, large lipid core, neovascularity, and aggregation of macrophages releasing inflammatory cytokines and proteases, including matrix metalloproteinases (MMPs). Plaques with a necrotic core >10% of their volume are highly susceptible to disruption, causing an ischemic event [2,3,4,5]. The local increase in MMP secretion contributes to plaque destabilization through augmentation of collagen and elastin destruction and fibronectin cleavage.

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Results

Discussion

Conclusion