Altered antioxidant status in peripheral skeletal muscle of patients with COPD

AbstractDespite the growing field of interest in the role of pulmonary oxidative stress in chronic obstructive pulmonary disease (COPD), barely any data are available with respect to antioxidant capacity in the peripheral musculature of these patients. The main objective of this study was to assess in detail the antioxidant status in skeletal muscle of patients with COPD. Biopsies from the vastus lateralis of 21 patients with COPD and 12 healthy age-matched controls were analysed. Total antioxidant capacity, vitamin E, glutathione, and uric acid levels were determined and the enzyme activities of superoxide dismutase, glutathione reductase, glutathione peroxidase, and glutathione-S-transferase were measured. Malondialdehyde was measured as an index of lipid peroxidation. The total antioxidant capacity and the uric acid levels were markedly higher in COPD patients than in healthy controls (25%, P=0.006 and 24%, P=0.029, respectively). Glutathione-S-transferase activity was also increased (35%; P=0.044) in patients compared to healthy subjects. Vitamin E level was lower in patients than in controls (P<0.05). The malondialdehyde level was not different between the two groups. It can be concluded that the muscle total antioxidant capacity is increased in patients with COPD. Together with the reduced vitamin E levels, the increased glutathione-S-transferase activity and normal levels of lipid peroxidation products, these findings suggest that the antioxidant system may be exposed to and subsequently triggered by elevated levels of reactive oxygen species

Enhanced Sarcolemmal FAT/CD36 Content and Triacylglycerol Storage in Cardiac Myocytes From Obese Zucker Rats

International audienc

Separation and Determination of Fatty Acids from Lipid Fractions by High-Performance Liquid Chromatography: Cholesterol Esters of Umbilical Cord Arteries

Preeclampsia is accompanied by an extensive remodeling of the extracellular matrix of umbilical cord. It is associated with an increase in collagen content in the umbilical cord artery. Furthermore, preeclampsia distinctly reduces proteolytic and gelatinolytic activity, especially after activation with various agents

MitoQ improves mitochondrial dysfunction in heart failure induced by pressure overload.

Heart failure remains a major public-health problem with an increase in the number of patients worsening from this disease. Despite current medical therapy, the condition still has a poor prognosis. Heart failure is complex but mitochondrial dysfunction seems to be an important target to improve cardiac function directly. Our goal was to analyze the effects of MitoQ (100 µM in drinking water) on the development and progression of heart failure induced by pressure overload after 14 weeks. The main findings are that pressure overload-induced heart failure in rats decreased cardiac function in vivo that was not altered by MitoQ. However, we observed a reduction in right ventricular hypertrophy and lung congestion in heart failure animals treated with MitoQ. Heart failure also decreased total mitochondrial protein content, mitochondrial membrane potential in the intermyofibrillar mitochondria. MitoQ restored membrane potential in IFM but did not restore mitochondrial protein content. These alterations are associated with the impairment of basal and stimulated mitochondrial respiration in IFM and SSM induced by heart failure. Moreover, MitoQ restored mitochondrial respiration in heart failure induced by pressure overload. We also detected higher levels of hydrogen peroxide production in heart failure and MitoQ restored the increase in ROS production. MitoQ was also able to improve mitochondrial calcium retention capacity, mainly in the SSM whereas in the IFM we observed a small alteration. In summary, MitoQ improves mitochondrial dysfunction in heart failure induced by pressure overload, by decreasing hydrogen peroxide formation, improving mitochondrial respiration and improving mPTP opening

Changes in Cardiac Substrate Transporters and Metabolic Proteins Mirror the Metabolic Shift in Patients with Aortic Stenosis

In the hypertrophied human heart, fatty acid metabolism is decreased and glucose utilisation is increased. We hypothesized that the sarcolemmal and mitochondrial proteins involved in these key metabolic pathways would mirror these changes, providing a mechanism to account for the modified metabolic flux measured in the human heart. Echocardiography was performed to assess in vivo hypertrophy and aortic valve impairment in patients with aortic stenosis (n = 18). Cardiac biopsies were obtained during valve replacement surgery, and used for western blotting to measure metabolic protein levels. Protein levels of the predominant fatty acid transporter, fatty acid translocase (FAT/CD36) correlated negatively with levels of the glucose transporters, GLUT1 and GLUT4. The decrease in FAT/CD36 was accompanied by decreases in the fatty acid binding proteins, FABPpm and H-FABP, the β-oxidation protein medium chain acyl-coenzyme A dehydrogenase, the Krebs cycle protein α-ketoglutarate dehydrogenase and the oxidative phosphorylation protein ATP synthase. FAT/CD36 and complex I of the electron transport chain were downregulated, whereas the glucose transporter GLUT4 was upregulated with increasing left ventricular mass index, a measure of cardiac hypertrophy. In conclusion, coordinated downregulation of sequential steps involved in fatty acid and oxidative metabolism occur in the human heart, accompanied by upregulation of the glucose transporters. The profile of the substrate transporters and metabolic proteins mirror the metabolic shift from fatty acid to glucose utilisation that occurs in vivo in the human heart