Monocyte Phenotypes and Physical Activity in Patients with Carotid Atherosclerosis.

Atherosclerosis is associated with low-grade inflammation involving circulating monocytes. It has been shown that the levels of intermediate pro-inflammatory monocytes are associated with cardiovascular mortality and risk of ischemic stroke. It also has been shown that physical activity (PA) decreases inflammation markers, incidence of strokes, and mortality. In this cross-sectional study, we tested the effect of PA on circulating monocytes phenotype rate. A total of 29 patients with a carotid stenosis > 50% were recruited. Levels of physical activity (MET.min/week) were measured by the GPAQ questionnaire, arterial samples of blood were collected to analyze monocyte phenotype (classical, intermediate and non-classical) assessed by flow cytometry, and venous blood samples were used to dose antioxidant activity and oxidative damage. Antioxidant capacity was reduced and oxidative damage increased in patients. There was a significant decrease in the percentage of classical and intermediate monocytes in moderately active patients as compared with non-active and highly active patients. Inversely, the rate of non-classical monocytes increased in moderately active patients. Intense PA appears to blunt the beneficial effects of moderate PA. Our study also suggests that PA could be beneficial in such patients by reducing the rate of intermediate monocytes known to predict the risk of ischemic stroke and by increasing the non-classical monocytes involved in lesions' healing. Nevertheless, a longitudinal study would be necessary to confirm this hypothesis.

Lung oxidative stress and transcriptional regulations induced by estradiol and intermittent hypoxia.

We determined the effects of chronic intermittent hypoxia (CIH) and estradiol (E2) on oxidative stress and gene expression in the lungs. Female Sprague-Dawley rats were left intact (sham) or ovariectomized (OVX) and implanted with pumps delivering vehicle or E2 (0.5 mg/kg/day). Two weeks following surgery, the rats were exposed to room air (RA) or CIH for 7 days (10% O2, 10 cycles/hour, 8 h/day). Lung samples were used to measure the activities of pro- (NADPH and xanthine oxidases) and antioxidant (superoxide dismutase, catalase and glutathione peroxidase) enzymes, and concentrations of advanced oxidation of protein products (AOPP). We determined gene expression with an RNA microarray and enrichment analysis of differentially expressed genes. In rats exposed to RA, OVX and E2 supplementation increased pro- and antioxidant activities and AOPP concentration. In rats exposed to CIH, AOPP concentration, pro- and antioxidant enzymes activities increased in sham, did not changed in OVX-Veh rats, and were reduced in OVX-E2 rats. In rats exposed to RA, genes involved in extracellular matrix were up-regulated by OVX and down-regulated by E2, while E2 up-regulated genes involved in cell mobility/adherence and leukocytes migration. OVX downregulated expression of roughly 200 olfactory receptor genes without effect of E2. CIH altered gene expression in sham and OVX-E2, but not in OVX-Veh rats. Enrichment analysis confirmed the antioxidant effects of E2 under CIH. There are important interactions between ovarian hormones and CIH that can be relevant to better understand the consequences of sleep apnea (i.e. CIH) on the occurrence of lung pathologies in women.

Effects of Individualized Treadmill Endurance Training on Oxidative Stress in Skeletal Muscles of Transgenic Sickle Mice.

Oxidative stress is a key feature in the pathophysiology of sickle cell disease. Endurance training has been shown to reduce oxidative stress in the heart and the liver of sickle mice. However, the effects of endurance training on skeletal muscles, which are major producers of reactive oxygen species during exercise, are currently unknown. The aim of this study was to evaluate the effect of sickle genotype on prooxidant/antioxidant response to individualized endurance training in skeletal muscles of sickle mice. Healthy and homozygous Townes sickle mice were divided into trained or sedentary groups. Maximal aerobic speed and V̇O2 peak were determined using an incremental test on a treadmill. Trained mice ran at 40% to 60% of maximal aerobic speed, 1 h/day, 5 days/week for 8 weeks. Oxidative stress markers, prooxidant/antioxidant response, and citrate synthase enzyme activities were assessed in the gastrocnemius, in the plantaris, and in the soleus muscles. Maximal aerobic speed and V̇O2 peak were significantly reduced in sickle compared to healthy mice (-57% and -17%; p < 0.001). NADPH oxidase, superoxide dismutase, and catalase activities significantly increased after training in the gastrocnemius of sickle mice only. A similar trend was observed for citrate synthase activity in sickle mice (p = 0.06). In this study, we showed an adaptive response to individualized endurance training on the prooxidant/antioxidant balance in the gastrocnemius, but neither in the plantaris nor in the soleus of trained sickle mice, suggesting an effect of sickle genotype on skeletal muscle response to endurance treadmill training.

Protective roles of estradiol against vascular oxidative stress in ovariectomized female rats exposed to normoxia or intermittent hypoxia.

AIM: We tested the hypothesis that estradiol (E2 ) reduces aortic oxidative stress and endothelial dysfunction in ovariectomized (OVX) female rats exposed to room air (RA) or chronic intermittent hypoxia (CIH). METHODS: We used intact or OVX female rats treated with vehicle or E2 (0.5 mg/kg/d) and exposed to RA or CIH (21%-10% O2 , 10 cycles/h, 8 h/d) for 7 or 35 days, and measured the arterial pressure, heart rate and plasma endothelin-1 levels. We also measured in thoracic aortic samples, the activities of the pro-oxidant enzymes NADPH (NOX) and xanthine oxidase (XO), the antioxidant enzymes superoxide dismutase, catalase, glutathione peroxidase and the advanced oxidation protein products (AOPP-oxidative stress marker). Finally, we used aortic rings to assess the contractile response to phenylephrine and the vasodilatory response to acetylcholine. RESULTS: After 7 or 35 days of CIH, E2 supplementation reduced arterial pressure. E2 reduced plasma endothelin-1 levels after 7 days of CIH, but not after 35 days. Ovariectomy, but not CIH for 7 days, increased aortic oxidative stress and E2 treatment prevented this effect. Remarkably, in animals exposed to RA, this was achieved by a reduction in NOX and XO activities, but in animals exposed to CIH this was achieved by increased catalase activity. In OVX female rats exposed to CIH for 7 days, E2 supplementation improved the NO-mediated vasodilation. After 35 days of CIH, enzymatic activities, AOPP and aortic reactivity were similar in all groups. CONCLUSION: E2 -based therapy could help prevent the vascular consequences of CIH in apneic women.