Increased atherosclerosis in myeloperoxidase-deficient mice

Dual Functionality of Myeloperoxidase in Rotenone-Exposed Brain-Resident Immune Cells

“…Mice lacking MPO have a significantly increased incidence of experimental autoimmune encephalomyelitis 53 and show increased atherosclerosis and enhanced lung inflammation. 54,55 Similarly, there is a greater occurrence of severe infections and chronic inflammatory processes among MPO-deficient patients. 56 In contrast, blockade of MPO activity in mouse models and in humans can reduce the pathological response in diseases such as PD and in pathological conditions such as renal ischemia.…”

A genotypic association implicates myeloperoxidase in the progression of hepatic fibrosis in chronic hepatitis C virus infection

“…Consistent with that concept, disruption of the MPO gene in mice led to exacerbated atherosclerosis, 30 and increased incidence of experimental autoimmune encephalomyelitis, a CD4 T cell mediated demyelinating disease which is a model for multiple sclerosis. 31 A number of studies now suggest that MPO genotype is differentially associated with various disease states. The GG genotype has been associated with increased incidence of myeloid leukemia, 13 multiple sclerosis (females), 20 Alzheimer's disease (females), 15 lung cancer 17 (males), 26 aerodigestive tract cancers, 21,22 and gastrointestinal complications in chronic granulomatous disease, 25 while the GA/AA genotypes have been associated with increased risk in aging Finnish males for Alzheimer's disease 12 and lung cancer.…”

High insulin enhances neutrophil transendothelial migration through increasing surface expression of platelet endothelial cell adhesion molecule-1 via activation of mitogen activated protein kinase

“…The PMN transendothelial migration enhanced by high insulin might account for the high incidence of atherosclerotic diseases such as AMI and stroke in patients with diabetes, because PMN transendothelial migration seems to contribute to the formation of atherosclerotic plaques and their disruption [4,13]. There is growing evidence supporting a close relation between atherosclerosis and PMN activation and migration [11,12,22,23,24,25,26,27]. Firstly, atherosclerosis has been reported to be characterized by monocyte infiltration which can be mediated by the neutrophil-induced release of endothelial monocyte-chemoattractant protein-1 [22].…”

“…Firstly, atherosclerosis has been reported to be characterized by monocyte infiltration which can be mediated by the neutrophil-induced release of endothelial monocyte-chemoattractant protein-1 [22]. Secondly, some investigators suggested that the activity of MPO, which is an enzyme from leukocytes including neutrophils, was correlated with the presence of AMI, and MPO itself was present in atherosclerotic plaques [12,23]. Thirdly, recent reports indicated that neutrophils are occasionally found in disrupted plaques and also that they migrate into the arterial wall shortly after ischaemia-reperfusion [11,24].…”

“…Although the crucial early events in vascular inflammation in atherosclerosis are the adhesion and transendothelial migration of leukocytes, especially neutrophils, which are the first immune cells to arrive at the inflammatory site, seem to play important roles in the initiation of both events [10]. In addition, recent reports suggested that neutrophils were occasionally found in disrupted plaques [11], and myeloperoxidase (MPO), the enzyme of leukocytes (including neutrophils) which promotes oxidation of lipoproteins, was present in atherosclerotic plaques [12]. These observations support the importance of neutrophil transendothelial migration in the development and disruption of atherosclerotic plaques [13].…”