The myeloperoxidase (MPO) system of activated phagocytes is central to normal host defense mechanisms, and dysregulated MPO contributes to the pathogenesis of inflammatory disease states ranging from atherosclerosis to cancer.
In this study, we enrolled 1746 type 2 diabetic subjects, determined 4 common genetic variants related to oxidative stress (glutamate-cysteine ligase modifier subunit (GCLM) C-588T, myeloperoxidaseG-463A, human paraoxonase 1 Gln192Arg and NAD(P)H oxidase p22phox C242T polymorphisms), and measured carotid intima-media thickness (IMT) as a surrogate marker for atherosclerosis.
Paradoxically, MPO-deficient mice have been reported to show increased atherosclerosis compared with wild mice, although higher MPO levels are thought to exacerbate atherosclerotic disease.
Our observations indicate that expression of human MPO in macrophages promotes atherosclerosis in hypercholesterolemic mice, raising the possibility that the enzyme might be a potential therapeutic target for preventing cardiovascular disease in humans.
The mouse MPO gene, which lacks the primate-specific AluRRE, was unresponsive to PPARgamma ligands, suggesting the human MPO transgenes will enhance the utility of mouse models for diseases involving MPO, such as atherosclerosis and Alzheimer's.
The atherosclerosis severity score (ASC) for abdominal aorta and carotid arteries was determined by ultrasonography, and the MPO genotype was analyzed.
The aim of this study was to determine whether there is an association between MPO polymorphisms and brain infarction (BI), one of the main consequences of atherosclerosis.
In this investigation, we studied 120 AR patients and 90 matched controls to elucidate the association between polymorphisms in some metabolizing genes (GSTM1, GSTT1, CYP2E1, mEH, PON1, and MPO) and susceptibility to AR.
The evidence supporting a role for MPO in the pathogenesis of atherosclerosis, demyelinating diseases of the central nervous system, and specific cancers is reviewed and some of the new questions raised by these studies are discussed.
Considering the potential role of MPO in the process of atherosclerosis, studying the relationship between this polymorphism and the incidence of coronary artery disease (CAD) seems reasonable.
Evidence is accumulating that myeloperoxidase-derived oxidants modify biologic macromolecules and cell-regulatory pathways and that they play a role in atherosclerosis.