Myeloperoxidase modulation by LDL apheresis in Familial Hypercholesterolemia

Mariarita Puntoni,Francesco Sbrana,Tiziana Sampietro,Federico Bigazzi,Ezio Ferdeghini,Fabrizio Minichilli

doi:10.1186/1476-511x-10-185

Mariarita Puntoni, Francesco Sbrana + Show 4 more

Open Access

https://doi.org/10.1186/1476-511x-10-185

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Abstract

BackgroundMyeloperoxidase (MPO) is a marker of plaque vulnerability and a mechanistic bridge between inflammation and cardiovascular disease, and thus is a suitable target for therapeutic strategy against cardiovascular disease.MethodsSince hypercholesterolemia is associated with atherosclerosis and inflammation, we tested whether MPO serum levels were up-regulated in Familial Hypercholesterolemia (FH) and whether acute reduction of total cholesterol (TC) would also reduce MPO concentration. FH subjects undergoing LDL-apheresis (LDL-A) treatment are a paradigmatic clinical model where TC rapidly plunges from extremely high to extremely low levels after selective LDL removal, and then spontaneously rebounds to baseline conditions. This clinical setting allows multiple intra-patient observations at different plasma TC concentrations. We measured MPO levels in serum by ELISA tests, and in peripheral leukocytes by immunofluorescence, to learn whether they were affected by the changes in TC levels. Serum MPO was measured before and serially up to the 14th day following LDL-A.ResultsIn both serum and peripheral leukocytes, MPO concentrations were i) higher than in sex- and age-matched healthy controls (p < 0.01); ii) decreased with TC reduction; iii) parallel with TC time course; iv) correlated with plasma TC. At regression analysis, plasma TC was the only variable considered that influenced MPO serum levels (β 0.022 ± 0.010, p < 0.0001).ConclusionsIn FH the MPO serum levels were modulated through changes in the TC concentrations carried out by LDL-A. Further study is needed to determine whether reduced MPO levels obtained by LDL-A could have any therapeutic impact.

Highlights

Myeloperoxidase (MPO) is a marker of plaque vulnerability and a mechanistic bridge between inflammation and cardiovascular disease, and is a suitable target for therapeutic strategy against cardiovascular disease
Based on the above considerations, we addressed the questions whether hypercholesterolemia is associated with MPO up-regulation and whether MPO serum levels are affected by cholesterol modulation
As expected, compared to controls, patients’ lipid profiles were characterized by higher total cholesterol (TC) and LDL cholesterol (LDL-C) (p < 0.001); Acute phase reactant proteins (APRs) values were higher in Familial Hypercholesterolemia (FH) than in controls; patients’ MPO concentrations resulted in a tenfold increase relative to controls

Summary

Introduction

Myeloperoxidase (MPO) is a marker of plaque vulnerability and a mechanistic bridge between inflammation and cardiovascular disease, and is a suitable target for therapeutic strategy against cardiovascular disease. High concentrations of myeloperoxidase (MPO) are associated with atherosclerotic disease, marking its presence and severity [1], and is co-localized with its pro-oxidant products in atheroma [2,3]. Subjects with total or subtotal MPO deficiency, a defect with a frequency of about 1 in 2000-4000 Caucasians, have lower incidence of coronary artery disease (CAD) [4]. A functional polymorphism in the MPO promoter gene, which leads to a twofold reduction in MPO expression, is associated with a lower risk for angiographic evidence of CAD [5], nonfatal myocardial infarction and cardiac death [6,7,8]. MPO is a major antibacterial component that produces hypochlorous acid (HOCl), a potent oxidant originating from chlorous ion (Cl-) and hydrogen peroxide (H2O2) [14,15], and is secreted following activation of leukocytes.

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