Arginase activity and nitric oxide levels in patients with obstructive sleep apnea syndrome.

OBJECTIVE: Obstructive sleep apnea syndrome is characterized by repetitive obstruction of the upper airways, and it is a risk factor for cardiovascular diseases. There have been several studies demonstrating low levels of nitric oxide in patients with obstructive sleep apnea syndrome compared with healthy controls. In this study, we hypothesized that reduced nitric oxide levels would result in high arginase activity. Arginase reacts with L-arginine and produces urea and L-ornithine, whereas L-arginine is a substrate for nitric oxide synthase, which produces nitric oxide. METHODS: The study group consisted of 51 obstructive sleep apnea syndrome patients (M/F: 43/8; mean age 49±10 years of age) and 15 healthy control subjects (M/F: 13/3; mean age 46±14 years of age). Obstructive sleep apnea syndrome patients were divided into two subgroups based on the presence or absence of cardiovascular disease. Nitric oxide levels and arginase activity were measured via an enzyme-linked immunosorbent assay of serum samples. RESULTS: Serum nitric oxide levels in the control subjects were higher than in the obstructive sleep apnea patients with and without cardiovascular diseases (p<0.05). Arginase activity was significantly higher (p<0.01) in obstructive sleep apnea syndrome patients without cardiovascular diseases compared with the control group. Obstructive sleep apnea syndrome patients with cardiovascular diseases had higher arginase activity than the controls (p<0.001) and the obstructive sleep apnea syndrome patients without cardiovascular diseases (p<0.05). CONCLUSION: Low nitric oxide levels are associated with high arginase activity. The mechanism of nitric oxide depletion in sleep apnea patients suggests that increased arginase activity might reduce the substrate availability of nitric oxide synthase and thus could reduce nitric oxide levels.

Arginase activity and nitric oxide levels in patients with obstructive sleep apnea syndrome

OBJECTIVE: Obstructive sleep apnea syndrome is characterized by repetitive obstruction of the upper airways, and it is a risk factor for cardiovascular diseases. There have been several studies demonstrating low levels of nitric oxide in patients with obstructive sleep apnea syndrome compared with healthy controls. In this study, we hypothesized that reduced nitric oxide levels would result in high arginase activity. Arginase reacts with L-arginine and produces urea and L-ornithine, whereas L-arginine is a substrate for nitric oxide synthase, which produces nitric oxide. METHODS: The study group consisted of 51 obstructive sleep apnea syndrome patients (M/F: 43/8; mean age 49±10 years of age) and 15 healthy control subjects (M/F: 13/3; mean age 46±14 years of age). Obstructive sleep apnea syndrome patients were divided into two subgroups based on the presence or absence of cardiovascular disease. Nitric oxide levels and arginase activity were measured via an enzyme-linked immunosorbent assay of serum samples. RESULTS: Serum nitric oxide levels in the control subjects were higher than in the obstructive sleep apnea patients with and without cardiovascular diseases (p<0.05). Arginase activity was significantly higher (p<0.01) in obstructive sleep apnea syndrome patients without cardiovascular diseases compared with the control group. Obstructive sleep apnea syndrome patients with cardiovascular diseases had higher arginase activity than the controls (p<0.001) and the obstructive sleep apnea syndrome patients without cardiovascular diseases (p<0.05). CONCLUSION: Low nitric oxide levels are associated with high arginase activity. The mechanism of nitric oxide depletion in sleep apnea patients suggests that increased arginase activity might reduce the substrate availability of nitric oxide synthase and thus could reduce nitric oxide levels. .

Obstructive sleep apnea is associated with fatty liver and abnormal liver enzymes: a meta-analysis.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with the cluster of clinical conditions that comprise the metabolic syndrome, including nonalcoholic fatty liver disease (NAFLD). Our primary purpose was to estimate the effect of OSA on serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Our secondary purpose was to investigate the potential influence of OSA on histological severity of NAFLD to explore whether chronic intermittent hypoxia is associated with inflammation and fibrosis. METHODS: Our literature search identified 11 studies, from which we extracted information about numbers of control subjects and OSA patients, and ALT, AST, and NAFLD. RESULTS: From a total of 668 OSA patients and 404 controls, we found that the standardized difference in mean values of ALT and AST levels in patients with OSA was significantly different from that in the controls. Meta-regression showed that the association was independent of body mass index and type 2 diabetes. Fatty liver was associated with OSA in five studies with 400 subjects. OSA was significantly associated with liver fibrosis in 208 subjects, but not with lobular inflammation. CONCLUSIONS: Routine assessment of liver enzymes and liver damage should be implemented in OSA patients because they have an increase of 13.3% of ALT and 4.4% of AST levels, and a 2.6-fold higher risk of liver fibrosis when they have NAFLD, which is 2.6 times more frequent in OSA patients.

24 bp duplication of CHIT1 gene and determinants of human chitotriosidase activity among participants of EPISONO, a population-based cross-sectional study, São Paulo, Brazil.

OBJECTIVES: We investigated whether plasma chitotriosidase activity is related to Obstructive Sleep Apnea (OSA) conditions and is correlated with biochemical variables present in the EPISONO database. This is the first study conducted in an epidemiological and nutritional transition country using subjects from the EPISONO population-based cross-sectional study. DESIGN AND METHODS: Chitotriosidase (CHIT) activity was determined by fluorimetric assay. OSA classification was defined as an apnea-hypopnea index. The correlations were investigated using a multiple regression linear model and statistical criteria, with CHIT as the dependent variable and correlated variables (from the EPISONO database) as independent variables, to access the contribution of each one to the variation in CHIT activity. RESULTS: No significant difference was observed when comparing the mean CHIT activities of different apnea groups. The prevalence of the CHIT1 24-bp duplication from patients with severe apnea was higher than in controls. In a multiple regression linear model, CHIT concentration was positively associated with age, creatine and testosterone. Age was the strongest predictor of CHIT variation, followed by gender, waist circumference and TNFα levels. The whole regression model explained 14% of the CHIT variation. CONCLUSION: Many variables are related to CHIT activity and show evidence of the multifactor and potentially synergistic character of this enzyme. In this study, we found that age, gender, TNFα, Hcy, sleep efficiency and waist circumference were responsible for approximately 14% of CHIT variation. Further studies are needed to elucidate additional parameters that may be related to CHIT activity.

Lack of association of ACE gene I/D polymorphism with obstructive sleep apnea syndrome in Turkish patients.

Angiotensin-converting enzyme (ACE) is a vital enzyme in the renin-angiotensin-aldosterone system, and there are reports in the literature describing its role in the development of cardiovascular system diseases, with I/D polymorphism of the ACE gene. We examined the relationship between a patient group with obstructive sleep apnea syndrome (OSAS) and a control group in terms of I/D polymorphism of the ACE gene. We examined 64 patients, with 37 individuals serving as the control group. PCR was used to detect ACE I/D gene polymorphism. Genotype was determined according to the bands that formed on agarose gel electrophoresis. Among the 64 OSAS patients, 27 were identified with the ID genotype, 27 with the DD genotype and 10 with the II genotype; among the 37 control subjects, 19 were identified with the ID genotype, 11 with the DD genotype and 7 with the II genotype. When the case group and controls were compared in terms of ID, II and DD genotypes, no significant difference was observed. On the other hand, when the two groups were compared with respect to mean body mass index, the OSAS group was found to be significantly different from the control group (P = 0.009). We conclude that ACE I/D gene polymorphism is not a genetic risk factor for OSAS in Turkish patients.

The influence of obstructive sleep apnea on the expression of glycerol-3-phosphate dehydrogenase 1 gene.

Glycerol-3-phosphate dehydrogenase 1 (GPD1) is considered to be a key enzyme that connects carbohydrate and lipid metabolism. This gene is induced in response to sleep deprivation, suggesting a potential role for this enzyme in the manifestation of obstructive sleep apnea (OSA). This study aims to examine the effects of sleep apnea, obesity and other relevant clinical parameters on GPD1 expression in the peripheral blood of a rigorously selected sample population in order to identify a biological marker that would allow for early intervention and prevention of the disorder. Clinical and sleep parameters were assessed by a complete full-night polysomnography and the expression of GPD1 at the mRNA level was determined. The results were compared among 20 OSA patients and 20 controls, further classified into two subgroups according to their body mass index. The expression levels of the GPD1 gene did not differ between patients with OSA and their matched controls. The results were not affected by the clinical and biochemical measurements, the sleep parameters or the severity of nocturnal hypoxemia. On the other hand, individuals with OSA had higher levels of fasting glucose when compared with weight-matched controls (P = 0.01). Moreover, higher very low-density lipoprotein (VLDL) was found in the over-weight OSA patient group, and higher cholesterol levels were found in the eutrophic OSA group when compared with their respective controls (P < 0.05). Based on logistic regression analyses, fasting glucose levels emerged as an independent factor for OSA in both the eutrophic (odds ratio [OR] = 1.27; 95% confidence interval [CI] = 1.00-1.59) and over-weight groups (OR = 1.29; 95% CI = 1.04-1.59). Although the results from the current study corroborate the growing body of data connecting OSA to altered glucose metabolism, it does not provide evidence for the modulation of GPD1 transcription by either OSA or its related phenotypes. This suggests that GPD1 may not play a major role in the OSA manifestation.