Increased Myeloperoxidase Expression is Associated with Increase in Intra-Plaque Hemorrhage, Iron Content, Inflammation and Neovascularization in Diabetic Atherosclerosis: Implications for Plaque Progression

Abstract

Background: Myeloperoxidase (MPO), a heme peroxidase enzyme produced by macrophages, is a marker of oxidative stress associated with increased cardiovascular events in Diabetes Mellitus (DM). In this study we hypothesize that MPO protein and gene expression is associated with increased Intra-Plaque Hemorrhage (IPH), iron deposition, plaque inflammation and neovascularization in DM atheroma. Methods: Twenty-six human aortas with advanced plaques (14 DM vs.12 No-DM) were studied. MPO protein and gene expression were quantified with immunohistochemistry and RT-PCR respectively. IPH was evaluated using H&E stain. Plaque iron was scored using Perl’s stain and graded Inflammatory cells and neovessels were manually counted in parallel sections using with (CD68 and CD3), and (CD34) using immunohistochemistry method. Results: Total plaque MPO protein expression density (973.13 ± 28.32 vs. 356.24 ± 26.95; p = 0.0001) and MPO gene expression (0.00267 ± 0.0007 vs. 0.00033 ± 0.0001; p = 0.0001), IPH percentage (57.1% vs. 16.7 %; p= 0.04), iron grade (0.79 ± 0.21 vs. 0.25 ± 0.13; p = 0.05), inflammatory cell grade (1.71 ± 0.10 vs. 1.17 ± 0.11; p = 0.001) and total neovessel content (48.96 ± 4.68 vs. 21.54 ± 2.27; p = 0.0001) were significantly increased in DM plaques when compared to no-DM. Conclusion: Increased MPO protein and gene expression are associated with a parallel increase in IPH, iron grade, inflammation grade and neovessel content in DM. This suggests a possible role of MPO in enhancing the IPH, iron deposition; inflammation and neovascularization in high risk DM plaques may possibly due to oxidative stress.