Myeloperoxidase induces monocyte migration and activation after acute myocardial infarction.

Introduction: Myocardial infarction (MI) is a significant contributor to morbidity and mortality worldwide. Many individuals who survive the acute event continue to experience heart failure (HF), with inflammatory and healing processes post-MI playing a pivotal role. Polymorphonuclear neutrophils (PMN) and monocytes infiltrate the infarcted area, where PMN release high amounts of the heme enzyme myeloperoxidase (MPO). MPO has numerous inflammatory properties and MPO plasma levels are correlated with prognosis and severity of MI. While studies have focused on MPO inhibition and controlling PMN infiltration into the infarcted tissue, less is known on MPO's role in monocyte function. Methods and results: Here, we combined human data with mouse and cell studies to examine the role of MPO on monocyte activation and migration. We revealed a correlation between plasma MPO levels and monocyte activation in a patient study. Using a mouse model of MI, we demonstrated that MPO deficiency led to an increase in splenic monocytes and a decrease in cardiac monocytes compared to wildtype mice (WT). In vitro studies further showed that MPO induces monocyte migration, with upregulation of the chemokine receptor CCR2 and upregulation of inflammatory pathways identified as underlying mechanisms. Conclusion: Taken together, we identify MPO as a pro-inflammatory mediator of splenic monocyte recruitment and activation post-MI and provide mechanistic insight for novel therapeutic strategies after ischemic injury.

The 24-h profile of the DNA repair enzyme 8-oxoguanine glycosylase 1 (OGG1) is associated with age, TNF-α, and waist circumference in healthy adults.

It is unknown how the DNA repair enzyme OGG1 relates to healthy aging in humans, in particular to inflammaging, that is associated with increased levels of TNF-α. This study aimed (1) to investigate how 24-h profiles for OGG1 change during healthy aging and (2) to analyze the relationship of OGG1 with TNF-α, central body fat, cortisol and oxidative DNA/RNA damage. In a cross-sectional study in 20 healthy older and 20 young women, salivary levels of OGG1, TNF-α, cortisol and oxidative DNA/RNA damage were quantified by ELISAs every 4 h for a 24-h period. Trunk circumferences were taken as measures of central body fat. Older women, compared to young women, exhibited significantly lower protein levels of OGG1 throughout the whole 24-h period, a 2.5 times lower 24-h mean level for OGG1 (P < 0.00001) and loss of 24-h variation of OGG1. Both age groups demonstrated significant 24-h variation for TNF-alpha, cortisol and oxidative damage. The 24-h mean level for TNF-α was more than twice as high in older compared to young women (P = 0.011). Regression analysis detected that age, TNF-α and waist circumference were negative significant predictors of OGG1, explaining 56% of variance of OGG1 (P < 0.00001), while levels of cortisol and oxidative damage were no predictors of OGG1. Results indicate a strong decrease of protein levels of OGG1 and a loss of 24-h variation during natural cellular aging. The negative relationship, found between OGG1 and TNF-α and between OGG1 and waist circumference, suggests involvement of proinflammatory processes in DNA repair.