Protective effects of magnolol against oxidized LDL-induced apoptosis in endothelial cells

Magnolol, a compound extracted from the Chinese medicinal herb Magnolia officinalis, has several biological effects. However, its protective effects against endothelial injury remain unclear. In this study, we examined whether magnolol prevents oxidized low density lipoprotein (oxLDL)-induced vascular endothelial apoptosis. Incubation of oxLDL with magnolol (2.5-20 mu M) inhibited copper-induced oxidative modification via diene formation, thiobarbituric acid reactive substances (TBARS) assay and electrophoretic mobility assay. Apoptotic cell death as characterized by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) stain. We measured the production of reactive oxygen species (ROS) by using the fluorescent probe 2 ',7 '-dichlorofluorescein acetoxymethyl ester (DCF-AM), and observed the activity of antioxidant enzymes. Furthermore, several apoptotic signaling pathways which showed NF-kappa B activation, increased cytosolic calcium, alteration of mitochondrial membrane potential, cytochrome c release and activation of caspase 3 were also investigated. We demonstrated that magnolol prevented the copper-induced oxidative modification of LDL. Magnolol attenuated the oxLDL-induced ROS generation and subsequent NF-kappa B activation. Furthermore, intracellular calcium accumulation and subsequent mitochondrial membrane potential collapse, cytochome c release and activation of caspase 3 caused by oxLDL were also inhibited by magnolol. Our results suggest that magnolol may have clinical implications in the prevention of atherosclerotic vascular disease through decreasing the oxLDL-induced ROS production

Adipose proinflammatory cytokine expression through sympathetic system is associated with hyperglycemia and insulin resistance in a rat ischemic stroke model

Wang YY, Lin SY, Chuang YH, Chen CJ, Tung KC, Sheu WH. Adipose proinflammatory cytokine expression through sympathetic system is associated with hyperglycemia and insulin resistance in a rat ischemic stroke model. Am J Physiol Endocrinol Metab 300: E155-E163, 2011. First published October 26, 2010; doi:10.1152/ajpendo.00301.2010.Patients who experience acute ischemic stroke may develop hyperglycemia, even in the absence of diabetes, but the exact mechanisms are still unclear. Adipose tissue secretes numerous proinflammatory cytokines and is involved in the regulation of glucose metabolism. This study aimed to determine the effects of acute stroke on adipose inflammatory cytokine expression. In addition, because sympathetic activity is activated after acute stroke and catecholamines can regulate the expression of several adipocytokines, this study also evaluated whether alterations in adipose proinflammatory cytokines following acute stroke, if any, were medicated by sympathetic system. Acute ischemic brain injury was induced by ligating the right middle cerebral artery and bilateral common carotid arteries in male adult Sprague-Dawley rats. Adipose tumor necrosis factor-alpha (TNF-alpha) and monocyte chemoattractant protein-1 (MCP-1) mRNA and protein levels were determined by RT-PCR and enzyme-linked immunoassay, respectively. The stroke rats developed glucose intolerance on days 1 and 2 after cerebral ischemic injury. The fasting blood insulin levels and insulin resistance index measured by homeostasis model assessment were higher in the stroke rats compared with the sham group. Epididymal adipose TNF-alpha and MCP-1 mRNA and protein levels were elevated one-to twofold, in association with increased macrophage infiltration into the adipose tissue. When the rats were treated with a nonselective beta-adrenergic receptor blocker, propranolol, before induction of cerebral ischemic injury, the acute stroke-induced increase in TNF-alpha and MCP-1 was blocked, and fasting blood insulin concentration and homeostasis model assessment-insulin resistance were decreased. These results suggest a potential role of adipose proinflammatory cytokines induced by the sympathetic nervous system in the pathogenesis of glucose metabolic disorder in rats with acute ischemic stroke

Ginkgo biloba extract attenuates oxLDL-induced oxidative functional damages in endothelial cells

Ou HC, Lee WJ, Lee IT, Chiu TH, Tsai KL, Lin CY, Sheu WH. Ginkgo biloba extract attenuates oxLDL-induced oxidative functional damages in endothelial cells. J Appl Physiol 106: 1674-1685, 2009. First published February 19, 2009; doi:10.1152/japplphysiol.91415.2008.-Atherosclerosis is a chronic inflammatory process with increased oxidative stress in vascular endothelium. Ginkgo biloba extract (GbE), extracted from Ginkgo biloba leaves, has commonly been used as a therapeutic agent for cardiovascular and neurological disorders. The aim of this study was to investigate how GbE protects vascular endothelial cells against the proatherosclerotic stressor oxidized low-density lipoprotein (oxLDL) in vitro. Human umbilical vein endothelial cells (HUVECs) were incubated with GbE (12.5-100 mu g/ml) for 2 h and then incubated with oxLDL (150 mu g/ml) for an additional 24 h. Subsequently, reactive oxygen species (ROS) generation, antioxidant enzyme activities, adhesion to monocytes, cell morphology, viability, and several apoptotic indexes were assessed. Our data show that ROS generation is an upstream signal in oxLDL-treated HUVECs. Cu,Zn-SOD, but not Mn-SOD, was inactivated by oxLDL. In addition, oxLDL diminished expression of endothelial NO synthase and enhanced expression of adhesion molecules (ICAM, VCAM, and E-selectin) and the adherence of monocytic THP-1 cells to HUVECs. Furthermore, oxLDL increased intracellular calcium, disturbed the balance of Bcl-2 family proteins, destabilized mitochondrial membrane potential, and triggered subsequent cytochrome c release into the cytosol and activation of caspase-3. These detrimental effects were ameliorated dose dependently by GbE (P < 0.05). Results from this study may provide insight into a possible molecular mechanism underlying GbE suppression of the oxLDL-mediated vascular endothelial dysfunction

Identification of type 2 diabetes loci in 433,540 East Asian individuals

Meta-analyses of genome-wide association studies (GWAS) have identified more than 240 loci that are associated with type 2 diabetes (T2D)1,2; however, most of these loci have been identified in analyses of individuals with European ancestry. Here, to examine T2D risk in East Asian individuals, we carried out a meta-analysis of GWAS data from 77,418 individuals with T2D and 356,122 healthy control individuals. In the main analysis, we identified 301 distinct association signals at 183 loci, and across T2D association models with and without consideration of body mass index and sex, we identified 61 loci that are newly implicated in predisposition to T2D. Common variants associated with T2D in both East Asian and European populations exhibited strongly correlated effect sizes. Previously undescribed associations include signals in or near GDAP1, PTF1A, SIX3, ALDH2, a microRNA cluster, and genes that affect the differentiation of muscle and adipose cells3. At another locus, expression quantitative trait loci at two overlapping T2D signals affect two genes—NKX6-3 and ANK1—in different tissues4–6. Association studies in diverse populations identify additional loci and elucidate disease-associated genes, biology, and pathways

A multi-ancestry genome-wide study incorporating gene-smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure

Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene–smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2. We report here 136 loci significantly associated with MAP and/or PP. Of these, 61 were previously published through main-effect analysis of BP traits, 37 were recently reported by us for systolic BP and/or diastolic BP through gene–smoking interaction analysis and 38 were newly identified (P < 5 × 10−8, false discovery rate < 0.05). We also identified nine new signals near known loci. Of the 136 loci, 8 showed significant interaction with smoking status. They include CSMD1 previously reported for insulin resistance and BP in the spontaneously hypertensive rats. Many of the 38 new loci show biologic plausibility for a role in BP regulation. SLC26A7 encodes a chloride/bicarbonate exchanger expressed in the renal outer medullary collecting duct. AVPR1A is widely expressed, including in vascular smooth muscle cells, kidney, myocardium and brain. FHAD1 is a long non-coding RNA overexpressed in heart failure. TMEM51 was associated with contractile function in cardiomyocytes. CASP9 plays a central role in cardiomyocyte apoptosis. Identified only in African ancestry were 30 novel loci. Our findings highlight the value of multi-ancestry investigations, particularly in studies of interaction with lifestyle factors, where genomic and lifestyle differences may contribute to novel findings

Metabolic Syndrome Exacerbating Ankle-Brachial Index in Asian Type 2 Diabetic Patients

The aim was to assess the association between metabolic syndrome (MetS) and ankle-brachial index (ABI) in Asians with or without diabetes. In this cross-sectional study, the components of MetS, lipid profiles, and ABI were assessed. A total 441 participants were enrolled, and the ABI was significantly lower (1.09 +/- 0.10 vs 1.12 +/- 0.13, P = .015) in participants with MetS (n = 269) as compared with those without MetS (n = 172). To dissect the influence of diabetes, these 2 groups were further categorized according to either diabetes or not. Ankle-brachial index was highest in participants with neither MetS nor diabetes and lowest in those with both MetS and diabetes (P value for trend < .001). Metabolic syndrome is also an independent risk factor for low ABI in participants with diabetes (P = .018). Thus, MetS is usually associated with lower ABI, most obvious in diabetic participants

Metabolic syndrome associated with habitual indulgence and dietary behavior in middle-aged health-care professionals

Aims/Introduction: Few studies, especially in Asia, have examined the relevance between metabolic syndrome (MetS), habitual indulgence and dietary behaviors in health-care professionals. The present study evaluates metabolic syndrome rate and its association with habitual indulgence (coffee, tea, alcohol and cigarette smoking) and diet behavior in health-care professionals. Materials and Methods: Information was collected from 514 health-care professionals (147 men, 367 women) who underwent routine physical examinations at a medical center in central Taiwan. Results: Mean age was 48 +/- 5 years for men and 45 +/- 4 years for women. Mean body mass index was 25.2 +/- 4.0 kg/m(2) for men and 22.5 +/- 3.4 kg/m(2) for women. The age-adjusted MetS rate among subjects was 24.8-11.7% in men and 7.8-5.4% in women, using two different definitions, respectively. The MetS rate among those who occasionally or frequently consumed tea was higher than among those who never consumed tea (P < 0.05). Although the proportion of subjects who had MetS differed among those with differing alcohol drinking habits (never, quit and current; P < 0.05), a posteriori comparisons showed no significant differences between the two groups. Compared with those who had never smoked, the rate was higher in former smokers and current smokers (P < 0.001). No significant association with coffee consumption was found. People with MetS often consumed sweetened beverages (P < 0.05), rarely read nutrition labels and seldom consumed dairy products. Conclusions: Health-care professionals who regularly consume tea, smoke, frequently have sweetened drinks, rarely read nutrition labels or rarely consume dairy products are at higher risk of suffering from MetS. (J Diabetes Invest, doi:10.1111/j.2040-1124.2010.00055.x, 2010

Effects of Xylooligosaccharides in Type 2 Diabetes Mellitus

The purpose of this study was to evaluate the effect of xylooligosaccharide (XOS) on the blood sugar, lipids and oxidative status in type 2 diabetes mellitus (DM). A total of 26 outpatient subjects of Taichung Veterans General Hospital, Taiwan, with HbA1c levels between 7.0 and 10.0% and triglyceride <400 mg/dL were enrolled in the present study. Subjects were supplemented with 4 g/d XOS (n=12) or a placebo (n=14) for 8 wk in a randomized double-blind clinical design. The results showed that the anthropometric values and nutrient intakes did not change during the experimental period. XOS supplementation not only reduced the glucose. HbA1c and fructosamine concentrations, but also decreased the levels of total cholesterol, low density lipoprotein (LDL) cholesterol, oxidized low density lipoprotein (ox-LDL) and apolipoprotein B. The activity of catalase of the erythrocyte sample decreased in the XOS group, but not the activities of superoxide dismutase and glutathione peroxidase. In conclusion, the dietary supplementation with XOS for 8 wk was effective in improving the blood Sugar and lipids in type 2 diabetes, indicating that XOS-containing diets might be beneficial to DM Subjects

Protective effects of eugenol against oxidized LDL-induced cytotoxicity and adhesion molecule expression in endothelial cells

Eugenol, a natural constituent of a number of aromatic plants and their essential oil fractions, has several biological effects. However, its protective effects against endothelial injury remain unclarified. This study investigates how eugenol affects human umbilical vein endothelial cells (HUVECs) dysfunction mediated by oxidized low density lipoprotein (oxLDL). Our results showed that the suppression of endothelial NO synthase (eNOS) expression, enhancement of adhesion molecules (ICAM, VCAM, and E-selectin) expression, and adherence of monocytic THP1 cells caused by a non-cytotoxic concentration (100 mu g/ml) of oxLDL were ameliorated following a eugenol treatment (12.5-100 mu M) in HUVECs. Eugneol also inhibited the reactive oxygen species (ROS) generation, intracellular calcium accumulation, and the subsequent mitochondrial membrane potential collapse, cytochrome c release and caspase-3 activation induced by oxLDL. The cytotoxicity and apoptotic features induced by a cytotoxic concentration (200 mu g/ml) of oxLDL was also attenuated by eugenol. Our results suggest that eugenol may protect against the oxLDL-induced dysfunction in endothelial cells. (c) 2006 Elsevier Ltd. All rights reserved