1.2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl) acetamide (PF-06282999) is a member of the thiouracil class of irreversible inactivators of human myeloperoxidase enzyme and a candidate for the treatment of cardiovascular disease.
MPO (myeloperoxidase) is a peroxidase enzyme secreted by activated leukocytes that plays a pathogenic role in cardiovascular disease, mainly by initiating endothelial dysfunction.
Myeloperoxidase (MPO) is a leukocyte-derived redox enzyme that has been linked to oxidative stress and damage in many inflammatory states, including cardiovascular disease.
Myeloperoxidase (MPO), a peroxidase enzyme, and alpha-1-acid glycoprotein (AGP), an acute-phase protein, are known to be released in patients with inflammatory conditions and cardiovascular disease (CVD).
Myeloperoxidase (MPO) as enzyme which oxidizes lipoproteins and paraoxonase1 (PON1) as anti-oxidative enzyme have been involved in pathogenesis of cardiovascular disease.
Myeloperoxidase (MPO) is highly enriched in neutrophils, can inhibit nitric oxide-mediated vasorelaxation in vitro and is associated with increased cardiovascular disease risk.
Activation of leukocytes and in particular polymorphonuclear neutrophils (PMN) has emerged as a critical confounder in the pathophysiology of cardiovascular disease: Myeloperoxidase (MPO), one of the principal proteins hosted in and secreted by activated PMN, has been mechanistically linked to endothelial and left ventricular (LV) dysfunction in rodent models of sepsis and ischemic cardiomyopathy.
Additionally, matrix metalloproteinase-8 concentration was associated with the risk for a coronary artery disease event, myocardial infarction and death, and myeloperoxidase concentration with the risk for cardiovascular disease events, stroke and death.
Elucidating the mechanisms by which elevated MPO leads to poor prognosis and conversely, investigating the beneficial effects of therapeutic MPO inhibition on alleviating disease phenotype, will facilitate future MPO-targeted clinical trials for improving CVD-related outcomes.
Height, weight, BMI, waist circumference, clinical and metabolic markers, adipokines, and inflammatory (PCR, IL-6, IL-8 and TNF-α) and CVD risk biomarkers (MPO, MMP-9, sE-selectin, sVCAM, sICAM, and PAI-1) were analyzed.
However, a lack of good animal models for examining the presence and catalytic activity of MPO in vascular lesions has impeded mechanistic studies into CKD-associated cardiovascular diseases.
In conclusion, intracellular monocyte myeloperoxidase was not associated with incident cardiovascular disease in this prospective population-based study.
In fully adjusted models, the highest versus lowest quartile of MPO/HDLp was associated with a 74% increase in incident ASCVD (aHR, 1.74, 95% CI 1.12-2.70) and a 91% increase in total incident CVD (aHR, 1.91, 95% CI 1.27-2.85).
No relationship between neutrophil granulocyte activation and the myeloperoxidase gene - 129 G>A and - 463 G>A promoter polymorphisms: implications for investigations of cardiovascular disease.
Our findings suggest that the -463 G-->A SNP, which supposedly results in lower MPO activity, is associated with a lower prevalence of CVD in ESRD patients.
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.
Our study suggests that in addition to mature MPO, circulating pro-MPO may cause oxidative modifications of proteins thereby contributing to cardiovascular disease.
Phagocyte-derived myeloperoxidase (MPO) and proinflammatory HDL are associated with metabolic syndrome (MetS) and increased cardiovascular disease risk.
Since MPO is suspected to be a bio-marker in cardiovascular disease, -638C > A and V53F polymorphisms associated with increased enzymatic activity could be genetic determinants for cardiovascular disease risk.
The level of MPO for the CON group was 84 ng/mL (73-87 ng/mL), for the ESRD group 77 ng/mL (11-89 ng/mL) and for the ESRD/CVD group 21 ng/mL (8-47 ng/mL), with a significant statistical difference of the ESRD/CVD group from the CON and ESRD groups (p<0.001).