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Cinnamaldehyde attenuates high glucose-induced oxidative stress and endothelial dysfunction as an Nrf2 activator
Abstracts / Atherosclerosis 252 (2016) e1ee196
Conclusions: Allele T of gene cx37 might be protective against macrovascular disease in women with diabetes mellitus type 2.
EAS16-0940, METABOLIC ABNORMALITIES AND ATHEROSCLEROSIS: DIABETES. LpPLA2 IN GESTATIONAL DIABETES MELLITUS e A PROTECTIVE SYSTEM FOR PLACENTA AND FETUS? C. Wadsack. Medical University of Graz, Department of Obstetrics and Gynecology, Graz, Austria Objectives: Gestational Diabetes Mellitus (GDM) and obesity are pregnancy conditions associated with low-grade inflammation in the placenta and fetus. In order to protect the feto-placental unit, anti-oxidative defense systems may have evolved. Placental macrophages (Hofbauer cells, HBCs) may contribute to these systems. Lipoprotein-associated phospholipase A2 (LpPLA2) -produced by macrophages is an enzyme with substrate preferance towards oxidized phospholipids (oxPL). We tested the hypothesis that LpPLA2 is secreted by HBCs, its presence in neonates and its regulation by the diabetic environment. Methods: Neonatal low (LDL) and high (HDL) density lipoprotein was isolated from cord blood and used for LpPLA2 activity assay, DHR assay and ELISAs assessing oxidative stress/protein modifications. Supernatant from control and diabetic primary HBCs were used for LpPLA2 mass/activity measurements and used for Multiplex to identify differently expressed cytokines. Results: In contrast to adults, LpPLA2 activity was higher on neonatal HDL than on LDL particles. GDM increased total neonatal plasma LpPLA2 activity. LpPLA2 activity on GDM HDL particles showed positive correlation with fetal cord blood insulin. HBCs showed an increase in LpPLA2 protein and activity upon insulin treatment. In term placental tissue LpPLA2 was found to be significantly elevated in GDM, this increase was paralleled by an increase in PAFR. GDM-HDL anti-oxidative potential was higher compared to controls. Conclusions: Placental LpPLA2 activity is regulated by metabolic hormones/cytokines in HBCs. oxPL-upregulation may represent a positive feedback circuit. Maternal low grade pro-inflammatory GDM/obesity are associated with increased LpPLA2 in HBCs and neonates. We speculate that LpPLA2 represents an anti-oxidative defense system for placenta and fetus.
EAS16-0852, METABOLIC ABNORMALITIES AND ATHEROSCLEROSIS: DIABETES. CINNAMALDEHYDE ATTENUATES HIGH GLUCOSE-INDUCED OXIDATIVE STRESS AND ENDOTHELIAL DYSFUNCTION AS AN NRF2 ACTIVATOR F. Wang, P. Wang, J. Wan, J. Hou, P. Zhou. The First Affiliated HospitalChengdu Medical College, Department of Cardiology, Chengdu, China Objectives: It is well documented that hyperglycemia-induced oxidative stress is an important causative factor of endothelial dysfunction. Cinnamaldehyde (CA) is a key flavor compound in cinnamon essential oil that can enhance the antioxidant defense against reactive oxygen species (ROS) by activating NF-E2-related factor 2 (Nrf2), which has been shown to have a cardiovascular protective effect, but its role in endothelial dysfunction induced by high glucose is unknown.
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NO levels in HUVECs, but these effects were reversed by Nrf2-siRNA in high glucose conditions. Conclusions: Our results indicated that CA protected endothelial dysfunction under high glucose conditions and this effect was mediated by Nrf2 activation and the up-regulation of downstream target proteins. CA administration may represent a promising intervention in diabetic patients who are at risk for vascular complications.
EAS16-0273, METABOLIC ABNORMALITIES AND ATHEROSCLEROSIS: DIABETES. ASSOCIATION OF DIFFERENT CHOLESTEROL HOMEOSTASIS PATTERNS WITH ABDOMINAL OBESITY IN PATIENTS WITH CORONARY ARTERY DISEASE c 1, V. Spasojevi c-Kalimanovska 1, A. Zeljkovi c 1, J. S. Vladimirov 1, T. Gojkovi c-Ivanovi c 1. 1 Faculty of Pharmacy, Veki c 1, D. Kalimanovska-Ostric 2, 3, Z. Jeli Department of Medical Biochemistry, Belgrade, Serbia; 2 Clinical Center of Serbia, Institute for Cardiovascular Diseases, Belgrade, Serbia; 3 University of Belgrade, School of Medicine, Belgrade, Serbia Objectives: Dyslipidemia represents a leading pathophysiological characteristic of obesity and a significant risk factor for subsequent coronary artery disease (CAD) development. Evaluation of cholesterol homeostasis by non-cholesterol sterols (NCSs) analysis may offer a comprehensive insight into the aforementioned disorders.Therefore, we investigated associations of these cholesterol homeostasis markers with the obesity development among healthy subjects and statin-naive and statin-treated CAD patients. Methods: The study included 78 CAD (47 statin-naive and 31 statintreated) patients and 31 controls (CG). NCSs were determined by GC-FID method. Results: Each participant’s group was divided into four synthesis/absorption patterns’ subgroups according to median values of lathosterol and b-sitosterol, representative cholesterol synthesis and absorption markers. BMI (body mass index) values did not differ among healthy subjects with poor synthesis and good absorption (PS/GAs) compared to those with good synthesis and poor absorption (GS/PAs), whereas the waist to hip ratio (W/ H) was significantly higher in the GS/PAs (p<0.05). Among statin-naive patients, GS/PAs had significantly higher BMI values and hip circumference compared to PS/GAs (p<0.01; p<0.05, respectively). Among statin-treated patients, GS/PAs (poor statin responders) had significantly higher BMI and waist circumference values compared to PS/GAs (good statin responders). In all groups lathosterol levels correlated positively with weight, BMI and waist circumference, while b-sitosterol values correlated negatively with BMI in patients and with weight and W/H in CG. Conclusions: In healthy weight individuals, lathosterol and b-sitosterol levels could identify those with increased risk for developing CAD. In statin-naive and statin-treated CAD patients, cholesterol homeostasis monitoring provides better understanding of pathological mechanisms underlying the obesity development.
EAS16-0025, METABOLIC ABNORMALITIES AND ATHEROSCLEROSIS: DIABETES. ASSOCIATION BETWEEN NT-PROBNP AND VISCERAL ADIPOSITY J. Suwa. St. Luke's International Hospital, Tokyo, Japan
Methods: Dissected male C57BL/6J mouse aortic rings and HUVECs were cultured in normal glucose(NG 5.5 mM) or high glucose(HG 30.0 mM) DMEM treatment with or without CA (10 mM). Results: Treatment with CA protected the endothelium relaxation, inhibited ROS generation and preserved nitric oxide (NO) levels in the endothelium of mouse aortas treated with high glucose . CA up-regulated Nrf2 expression, promoted its translocation to the nucleus‘and increased HO-1, NQO1, Catalase and Gpx1 expression under high glucose condition. The increased level of nitrotyrosine in HUVECs under high glucose was also attenuated by treatment with CA. Dihydroethidium (DHE) and DAF-2DA staining indicated that CA inhibited the ROS generation and preserved the
Objectives: N-terminal pro-BNP (NT-proBNP) is used to estimate cardiac dysfunction and atherosclerosis. However, recently the relationship with visceral adiposity has also been proposed. The objective of this study was to investigate the relationship between serum NT-proBNP and visceral adiposity. Methods: The study population comprised of 1530 individuals (1060 men; mean age 52.6±11.3 years ) who underwent an annual health check at our institute between 2011and 2015. Individuals who were treated with medication for hypertension were excluded. This study was a crosssectional analysis using clinically-relevant demographic and biochemical
Conclusions: Allele T of gene cx37 might be protective against macrovascular disease in women with diabetes mellitus type 2.
EAS16-0940, METABOLIC ABNORMALITIES AND ATHEROSCLEROSIS: DIABETES. LpPLA2 IN GESTATIONAL DIABETES MELLITUS e A PROTECTIVE SYSTEM FOR PLACENTA AND FETUS? C. Wadsack. Medical University of Graz, Department of Obstetrics and Gynecology, Graz, Austria Objectives: Gestational Diabetes Mellitus (GDM) and obesity are pregnancy conditions associated with low-grade inflammation in the placenta and fetus. In order to protect the feto-placental unit, anti-oxidative defense systems may have evolved. Placental macrophages (Hofbauer cells, HBCs) may contribute to these systems. Lipoprotein-associated phospholipase A2 (LpPLA2) -produced by macrophages is an enzyme with substrate preferance towards oxidized phospholipids (oxPL). We tested the hypothesis that LpPLA2 is secreted by HBCs, its presence in neonates and its regulation by the diabetic environment. Methods: Neonatal low (LDL) and high (HDL) density lipoprotein was isolated from cord blood and used for LpPLA2 activity assay, DHR assay and ELISAs assessing oxidative stress/protein modifications. Supernatant from control and diabetic primary HBCs were used for LpPLA2 mass/activity measurements and used for Multiplex to identify differently expressed cytokines. Results: In contrast to adults, LpPLA2 activity was higher on neonatal HDL than on LDL particles. GDM increased total neonatal plasma LpPLA2 activity. LpPLA2 activity on GDM HDL particles showed positive correlation with fetal cord blood insulin. HBCs showed an increase in LpPLA2 protein and activity upon insulin treatment. In term placental tissue LpPLA2 was found to be significantly elevated in GDM, this increase was paralleled by an increase in PAFR. GDM-HDL anti-oxidative potential was higher compared to controls. Conclusions: Placental LpPLA2 activity is regulated by metabolic hormones/cytokines in HBCs. oxPL-upregulation may represent a positive feedback circuit. Maternal low grade pro-inflammatory GDM/obesity are associated with increased LpPLA2 in HBCs and neonates. We speculate that LpPLA2 represents an anti-oxidative defense system for placenta and fetus.
EAS16-0852, METABOLIC ABNORMALITIES AND ATHEROSCLEROSIS: DIABETES. CINNAMALDEHYDE ATTENUATES HIGH GLUCOSE-INDUCED OXIDATIVE STRESS AND ENDOTHELIAL DYSFUNCTION AS AN NRF2 ACTIVATOR F. Wang, P. Wang, J. Wan, J. Hou, P. Zhou. The First Affiliated HospitalChengdu Medical College, Department of Cardiology, Chengdu, China Objectives: It is well documented that hyperglycemia-induced oxidative stress is an important causative factor of endothelial dysfunction. Cinnamaldehyde (CA) is a key flavor compound in cinnamon essential oil that can enhance the antioxidant defense against reactive oxygen species (ROS) by activating NF-E2-related factor 2 (Nrf2), which has been shown to have a cardiovascular protective effect, but its role in endothelial dysfunction induced by high glucose is unknown.
e145
NO levels in HUVECs, but these effects were reversed by Nrf2-siRNA in high glucose conditions. Conclusions: Our results indicated that CA protected endothelial dysfunction under high glucose conditions and this effect was mediated by Nrf2 activation and the up-regulation of downstream target proteins. CA administration may represent a promising intervention in diabetic patients who are at risk for vascular complications.
EAS16-0273, METABOLIC ABNORMALITIES AND ATHEROSCLEROSIS: DIABETES. ASSOCIATION OF DIFFERENT CHOLESTEROL HOMEOSTASIS PATTERNS WITH ABDOMINAL OBESITY IN PATIENTS WITH CORONARY ARTERY DISEASE c 1, V. Spasojevi c-Kalimanovska 1, A. Zeljkovi c 1, J. S. Vladimirov 1, T. Gojkovi c-Ivanovi c 1. 1 Faculty of Pharmacy, Veki c 1, D. Kalimanovska-Ostric 2, 3, Z. Jeli Department of Medical Biochemistry, Belgrade, Serbia; 2 Clinical Center of Serbia, Institute for Cardiovascular Diseases, Belgrade, Serbia; 3 University of Belgrade, School of Medicine, Belgrade, Serbia Objectives: Dyslipidemia represents a leading pathophysiological characteristic of obesity and a significant risk factor for subsequent coronary artery disease (CAD) development. Evaluation of cholesterol homeostasis by non-cholesterol sterols (NCSs) analysis may offer a comprehensive insight into the aforementioned disorders.Therefore, we investigated associations of these cholesterol homeostasis markers with the obesity development among healthy subjects and statin-naive and statin-treated CAD patients. Methods: The study included 78 CAD (47 statin-naive and 31 statintreated) patients and 31 controls (CG). NCSs were determined by GC-FID method. Results: Each participant’s group was divided into four synthesis/absorption patterns’ subgroups according to median values of lathosterol and b-sitosterol, representative cholesterol synthesis and absorption markers. BMI (body mass index) values did not differ among healthy subjects with poor synthesis and good absorption (PS/GAs) compared to those with good synthesis and poor absorption (GS/PAs), whereas the waist to hip ratio (W/ H) was significantly higher in the GS/PAs (p<0.05). Among statin-naive patients, GS/PAs had significantly higher BMI values and hip circumference compared to PS/GAs (p<0.01; p<0.05, respectively). Among statin-treated patients, GS/PAs (poor statin responders) had significantly higher BMI and waist circumference values compared to PS/GAs (good statin responders). In all groups lathosterol levels correlated positively with weight, BMI and waist circumference, while b-sitosterol values correlated negatively with BMI in patients and with weight and W/H in CG. Conclusions: In healthy weight individuals, lathosterol and b-sitosterol levels could identify those with increased risk for developing CAD. In statin-naive and statin-treated CAD patients, cholesterol homeostasis monitoring provides better understanding of pathological mechanisms underlying the obesity development.
EAS16-0025, METABOLIC ABNORMALITIES AND ATHEROSCLEROSIS: DIABETES. ASSOCIATION BETWEEN NT-PROBNP AND VISCERAL ADIPOSITY J. Suwa. St. Luke's International Hospital, Tokyo, Japan
Methods: Dissected male C57BL/6J mouse aortic rings and HUVECs were cultured in normal glucose(NG 5.5 mM) or high glucose(HG 30.0 mM) DMEM treatment with or without CA (10 mM). Results: Treatment with CA protected the endothelium relaxation, inhibited ROS generation and preserved nitric oxide (NO) levels in the endothelium of mouse aortas treated with high glucose . CA up-regulated Nrf2 expression, promoted its translocation to the nucleus‘and increased HO-1, NQO1, Catalase and Gpx1 expression under high glucose condition. The increased level of nitrotyrosine in HUVECs under high glucose was also attenuated by treatment with CA. Dihydroethidium (DHE) and DAF-2DA staining indicated that CA inhibited the ROS generation and preserved the
Objectives: N-terminal pro-BNP (NT-proBNP) is used to estimate cardiac dysfunction and atherosclerosis. However, recently the relationship with visceral adiposity has also been proposed. The objective of this study was to investigate the relationship between serum NT-proBNP and visceral adiposity. Methods: The study population comprised of 1530 individuals (1060 men; mean age 52.6±11.3 years ) who underwent an annual health check at our institute between 2011and 2015. Individuals who were treated with medication for hypertension were excluded. This study was a crosssectional analysis using clinically-relevant demographic and biochemical