bluuebunny/crossref_metadata_2025_split huggingface dataset:
Resveratrol Protects Against Angiotensin II‐Induced Cellular Hypertrophy through Inhibition of CYP1B1/Mid‐Chain Hydroxyeicosatetraenoic Acid Mechanism
Authors: Shoieb Sherif M. , El‐Kadi Ayman O. S. 
Published: June 2021

ObjectiveCytochrome P450 1B1 (CYP1B1) and its associated cardiotoxic mid‐chain hydroxyeicosatetraenoic acid (HETEs) metabolites have been reported to directly contribute to the development of cardiac hypertrophy. Resveratrol (RESV) is naturally occurring and commercially available polyphenol that possess beneficial effects in wide array of cardiovascular diseases. Several reports have shown the capacity of RESV to treat cardiac hypertrophy, myocardial infarction and heart failure. However, the underlying mechanisms, responsible for RESV beneficial effects, are not fully elucidated. Since RESV is a well‐known CYP1B1 inhibitor, the purpose of this study is to investigate whether RESV protects against angiotensin II (Ang II)‐induced cellular hypertrophy through inhibition of CYP1B1/mid‐chain HETEs mechanism.MethodsHuman ventricular cardiomyocytes RL‐14 and rat cardiomyoblast H9c2 cells were treated with vehicle or 10 μM Ang II in the absence and presence of 2, 10 or 50 μM RESV for 24 h. Thereafter, the level of mid‐chain HETEs was determined using liquid chromatography–mass spectrometry (LC/MS). Hypertrophic markers and CYP gene expression and protein levels were measured using real‐time PCR and Western blot analysis, respectively.ResultsOur results demonstrated that RESV, at concentrations of 10 and 50 μM, was able to protect against Ang‐II‐induced cellular hypertrophy as evidenced by a substantial inhibition of hypertrophic markers, β‐myosin heavy chain (MHC)/α‐MHC and atrial natriuretic peptide (ANP). Ang II significantly induced the protein expression of CYP1B1 and increased the metabolite formation rate of its associated mid‐chain HETEs namely 5‐, 8‐, 9‐, 12‐ and 15‐HETE in both cell lines. Interestingly, the protective effect of RESV, at concentrations 10 and 50 μM, was associated with a significant decrease of CYP1B1 protein expression and mid‐chain HETEs to nearly control levels.ConclusionOur results provided the first evidence that RESV protects against Ang II‐induced cellular hypertrophy, at least in part, through CYP1B1/mid‐chain HETEs‐dependent mechanism.Support or Funding InformationThis work was supported by a grant from the Canadian Institutes of Health Research [Grant 106665] to A.O.S.E. S.M.S. is the recipient of Antoine Noujaim Graduate Scholarship in Pharmaceutical Sciences.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
20‐HETE Antagonism Reduces Left Ventricular Remodeling Post‐Myocardial Infarction
Authors: D'Addario Catherine , Joseph Gregory , Soler Amanda , Brechoire Ines , Hutcheson Brenda , Falck John R , Proctor Spencer , Schwartzman Michal , Rocic Petra 
Published: June 2021

20‐Hydroxyeicosatetraenoic acid (20‐HETE) is a cytochrome p450‐derived eicosanoid that stimulates endothelial dysfunction and inflammation via binding to its receptor, GPR75 (GPCR‐Gαq/11). Increased 20‐HETE in animals and humans is associated with hypertension, stroke, myocardial infarction (MI), metabolic syndrome (MetS), and increased reactive oxygen species (ROS). However, investigated effectiveness of 20‐HETE antagonists on ROS generation and MI size has been limited by short‐term follow up and administration of inhibitors prior to onset of MI only in healthy animals. Here, we evaluated the effect of a 20‐HETE antagonist, 20‐SOLA, administered at onset of reperfusion on post MI remodeling 48 hours and 8 weeks after reperfusion in normal (SD) and MetS (JCR:LA‐cp) rats. 20‐HETE was elevated in response to ischemia and more so during reperfusion; this elevation was greater in MetS (ischemia: 2‐fold SD and JCR; reperfusion: 3‐fold SD, 4‐fold JCR). MI size was markedly greater in JCR vs. SD rate (50% vs. 25% of LV). Treatment with 20‐SOLA significantly decreased MI size in both SD (~50%) and JCR (~65%) rats. Equivalent results were obtained in animals treated with GPR75‐shRNA‐Lnv at onset of reperfusions. 20‐SOLA improved coronary blood flow (1.00 ± 0.01 to 1.84 ± 0.03 mg/ml/g in SD to 0.99 ± 0.03 to 1.75±0.01 mg/ml/g in JCR). Mechanistically, smaller MI size in 20‐SOLA‐treated animals correlated with decreased ROS production in JCR rats (90%). Furthermore, survival and left ventricular (LV) function were preserved 8 weeks post MI in 20‐SOLA‐treated animals (ejection fraction (EF) = 80.5% (SD, 100% survival) and 82.5% (JCR, 100% survival)). This correlated with decreased ROS, preserved myocyte morphology, and preserved intact collagen. Differential activation of MMPs in SD vs. JCR rats vs. 20‐SOLA‐treated animals underlie the observed morphological, structural and functional changes. ROS production was decreased in JCR rats treated with a NOX inhibitor (~60%); NOX inhibition also markedly reduced MI size at 48h (60%) and preserved LV function at 8 weeks (EF = 74%, 85% survival) vs. non‐treated rats demonstrating an important role for NOX‐derived ROS in determining MI size and long‐term post‐MI remodeling. In the aggregate, these results indicated that targeting 20‐HETE actions may be an important consideration in prevention of detrimental LV remodeling and mortality post MI. Funding: HL093052.Support or Funding InformationFunding: HL093052This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effect of Bauhinia variegata Leaf Extract in Diabetic Cardiomyopathy
Authors: Kulkarni Yogesh Anant , Laddha Ankit Pravin 
Published: June 2021

Diabetes mellitus is a chronic metabolic disorder associated with development of micro and macro vascular diabetic complications. According to World Health Organization cardiovascular disease causes up to 65% of deaths among diabetic population. The present work was designed to study effect of Bauhinia variegata, a medicinal plant described in Ayurveda for its medicinal benefits in diabetic cardiomyopathy. Alcoholic extract of Bauhinia variegata leaf (AlcE) was prepared by Soxhlet extraction technique and was standardized using HPTLC. Male Sprague Dawley rats were injected with streptozotocin (55 mg/kg, i.p.) for induction of diabetes. After 42 days of diabetes induction, the animals were grouped and treated with alcoholic extract at dose of 250, 500 and 1000 mg/kg by oral route for next 28 days. At the end of treatment, plasma and heart tissue were collected for evaluation of various parameters. AlcE at 1000 mg/kg significantly reduced plasma glucose as compared to diabetic control animals. AlcE at dose of 500 and 1000 mg/kg significantly (P<0.001) reduced elevated level of creatine kinase‐MB, lactate dehydrogenase and aspartate transaminase in plasma as compared to diabetic animals. AlcE treatment prevented cardiac tissue from oxidative damage, it significantly reduced the elevated level of malonyl dialdehyde at dose of 500 and 1000 mg/kg whereas it significantly increased the level of antioxidant enzymes at dose of 1000 mg/kg (P<0.001). Present study showed that Bauhinia variegata leaf extract has significant effect in management of diabetic cardiomyopathy.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Baicalein Neutralizes Hypercholesterolemia‐Induced Aggravation of Cardiac Oxidative Injury
Authors: Al‐Rejaie Salim Salih 
Published: June 2021

Hypercholesterolemia is a global well‐known contributing factor in cardiovascular diseases through provoking cardiac oxidative damage and depleting energy production. Baicalein (BL) is a bioactive polyphenolic flavonoid that has multiple cardiovascular beneficial effects. This study aims to investigate the potential cardio‐protective properties of BL against cardiac oxidative injury in high cholesterol diet (HCD) fed rats. HCD in pellet form was prepared by adding 1% cholesterol + 0.5% cholic acid with normal cholesterol rat chow powder. Eighteen animals were fed with HCD for 10 weeks. At the 6th week, twelve animals started BL treatment in two doses (25 and 50 mg/kg/day, orally). Histologically, BL protected the myocardial morphology against HCD associated multi‐focal vacuolar degeneration. BL markedly reduced serum total cholesterol (TC), triglycerides (TG), creatine kinase‐B (CK‐B), lactate dehydrogenase (LDH) and creatine kinase‐MB (CK‐MB) levels in hypercholesteremic rats. In cardiac tissue homogenate, the levels of lipid‐peroxidation biomarker, thiobarbituric acid reactive substances (TBARS) were significantly prohibited, while glutathione (GSH) levels were increased markedly by BL in HCD fed rats. In addition, hypercholesterolemia‐induced inhibition of cardiac enzymatic activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) was considerably attenuated by BL treatment. Overall, the current findings elucidated that BL exhibits a promising therapeutic value for cardiac metabolic changes linked with hypercholesterolemia via enhancement of the redox balance.Support or Funding InformationDeanship scientific research at King Saud UniversityThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Water‐pipe Smoke Negatively Distress Cardiovascular Biomarkers in Mice
Authors: Rababah Abeer , Bsoul Ragad , Alkhatatbeh Mohammad , Alzoubi Karem 
Published: June 2021

Tobacco use is one of the main risk factors to cardiovascular diseases (CVDs) and atherosclerosis in particular. It was mis‐considered that water‐pipe smoking (WPS) is less harmful than cigarette smoking due to its flavor. Studies had shown that more than 100 million people smoke waterpipe daily. WPS contains several toxic materials such as: nicotine, carcinogens, tar, carbon monoxide and heavy metals. Thus, WPS is considered to be as one of the toxic environmental factors that should be investigated intensively. The aim of this study is to investigate the effect of WPS on several cardiovascular biological markers that may cause atherosclerosis in mice. The study also conducted to study the temporal effects of WPS on the atherosclerotic biomarkers upon short (2 weeks) and long‐term (8 weeks) exposures. Mice were exposed to WPS and heart homogenates were analyzed to elucidate the effects of WPS on matrix metalloproteinase (MMPs), endothelin‐1 (ET‐1) and, myeloperoxidase (MPO). Following protein estimation, enzyme‐linked immunosorbent assays were done to measure the levels of MMPs (isoforms 1, 3, and 9), MPO, and ET‐1 protein. Our data showed that acute exposure to WPS significantly enhances the levels of MMP‐3, MMP‐9, and MPO expressions (p<0.05) compared to their corresponding control. However, the body was capable to compromise the levels for such parameters following continuous exposure for 8 weeks (p>0.05). Additionally, we showed that the level of ET‐1 was significantly higher upon chronic exposure to WPS compared to both control and acute exposure groups (p<0.05). In conclusion, WPS has a significant negative effect on cardiac health and the enhancement of the atherosclerotic biomarkers (MMP‐3 and 9, MPO, and ET‐1) might represent an early scavenger of compensatory efforts to maintain cardiac function after WP exposure.Support or Funding InformationThis project was supported by a grant from the Deanship of Research at Jordan University of Science and Technology (grant number 2015/249 to AR).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Deficiency of Sirtuin 3 Accentuates Angiotensin II‐Induced Arterial/Myocardial Stiffness and Hypertension
Authors: Chen Jian‐Xiong , Zeng Heng 
Published: June 2021

Hypertension is prevalent disease worldwide and is considered as the key factor for the development of heart failure with preserved ejection fraction (HFpEF). Arterial stiffness is the center feature of hypertension and has significant impact upon disease etiology and outcomes. Sirtuin 3 (SIRT3) emerged as a protein of particular interest to the aging and cardiovascular disease in humans. Our previous study has shown that deletion of SIRT3 resulted in impairment of coronary flow reserve (CFR) and diastolic dysfunction in mice. Little is known about role of SIRT3 in angiotensin II‐induced arterial stiffness and hypertension. In present study, wild type (WT) mice and SIRT3KO mice were infusion with Ang II (1000 ng/kg/min) for 4 weeks, blood pressure, pulse‐wave velocity (PWV), CFR and diastolic function (IVRT and MPI) were measured before and after Ang II treatment. Aorta and heart were collected and fibrosis were measured by Masson staining and fibroblast specific protein‐1 (FSP‐1) immunostaining. Our results revealed that Ang II infusion led to a significant increase in PWV, whereas knockout of SIRT3 further enhanced Ang II‐induced elevation of PWV. This was accompanied by increases in systolic, diastolic pressure and MAP in SIRT3KO mice + Ang II as compared to WT mice + Ang II. Knockout of SIRT3 further reduced CFR and increased IVRT and MPI in mice. Histologic and immunostaining studies revealed that Ang II‐induced aortic thickness and perivascular fibrosis were significantly increased in SIRT3KO mice compared to WT mice. Similarly, there were significant increase in Ang II‐induced fibrosis area and higher number of FSP‐1+ in the heart of SIRT3KO mice than WT mice. In addition, the expression of PDGF‐β was higher in the aorta and heart of SIRT3KO mice than WT mice. Double staining PDGF‐β with FSP‐1 showed an increased number of PDGF‐β+/FSP‐1+. Using NG2 pericyte tracing reporter NG2DsRedBAC mice, we further confirmed that Ang‐II‐induced NG2 pericyte recruitment was significantly increased in the SIRT3 KO mice, suggesting deletion of SIRT3 promotes Ang‐II‐induced pericyte recruitment which may differentiate into fibrosis and contribute to increased arterial and myocardial stiffness. Our study demonstrated that deletion of SIRT3 exacerbated Ang II‐induced arterial stiffness, hypertension and diastolic dysfunction. Deletion of SIRT3 increased arteries and myocardial stiffness via enhancing pericyte recruitment and pericytes‐to‐fibroblast transition.Support or Funding InformationThis work was supported by R01HL102042‐06This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Yerba Mate (Ilex paraguariensis) and Dimethyl Fumarate Can Improve Metabolic Syndrome Condition Induced by High Fat Diet in Mice
Authors: Valenca Samuel Santos , Valenca Helber Maia , Lanzetti Manuella 
Published: June 2021

IntroductionMetabolic syndrome (MS) is a combination of clinical signs and symptoms that occur together and directly contribute to the risk of developing cardiovascular disease and diabetes. Some studies suggest that the prevalence of MS in the US is 32% of the population, while in Brazil this level reaches 23%. The criteria for the classification of MS are diverse, but according to the WHO, the presence of diabetes or reduced glucose tolerance or insulin resistance, associated with at least two of the following conditions: elevation of blood pressure, dyslipidemia and obesity are considered. MS confers a two‐fold increased risk for developing cardiovascular disease, two to four times the risk of stroke, three to four times the risk of acute myocardial infarction. Our hypothesis is that toasted yerba mate and dimethyl fumarate have a therapeutic effect on the metabolic syndrome in mice.MethodsMetabolic syndrome was induced by hyperlipidic diet (60% of total calorie) in C57BL / 6 mice for 12 weeks, and treatment was performed concomitantly with yerba mate (2 mg / g) and dimethyl fumarate (0.24 mg / g) diluted in water, to which the animals had free access. The groups were separated as follows: control group (standard diet and water), HFD group (hyperlipidic diet and water), HFD + Mate group (hyperlipidic diet and mat herb tea) and HFD + DMF group (hyperlipidic diet and dimethyl fumarate).ResultsIt was observed that the HFD + Mate group obtained an increase in body mass in the same way as the HFD group, also increasing triglyceride levels, but maintained normal HDL levels. The HFD + DMF group, however, remained with body mass equal to the control group, maintaining normal levels of HDL and triglycerides. Both the HFD + Mate group and the HFD + DMF group remained at optimal glycemic levels, including glucose tolerance and insulin resistance tests. Histological analysis of the liver showed hepatic steatosis in the HFD group, but not in the HFD + Mate and HFD + DMF groups.ConclusionDMF was effective to prevent metabolic syndrome, once the hallmarks glucose, body weight, triglycerides and HDL cholesterol were kept similar to control group. DMF also protected against hepatic steatosis. About mate tea, the effect was more modest than DMF, once only HDL cholesterol and glucose were protected, as well as hepatic steatosis was avoided. These data suggest DMF can modulate satiation preventing the syndrome metabolic development.Support or Funding InformationBrazilian Research Agencies ‐ CAPES, CNPq and FAPERJThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Pre‐ and Postconditioning Effects of Forced Treadmill Running on Gastric Injury Induced by Indomethacin in Rats
Authors: Filaretova Ludmila , Komkova Olga , Punin Yuriy , Yarushkina Natalia 
Published: June 2021

The preconditioning effect of a mild stressor can reduce ulcerogenic effect of a severe stressor on the gastric mucosa. Our previous findings suggest that glucocorticoids produced in response to stress contribute to the gastroprotective effect of stress preconditioning and promote a healing of gastric injury. In this study, we tested if forced treadmill running can attenuate gastric injury induced by indomethacin (IM) in rats. IM administration (35 mg/kg, sc) in fasting (24 h) rats caused formation of gastric erosions (4 h after injection) that then gradually healed over the next 48 hours. Rats were subjected forced treadmill running (30 min) 1 h before IM administration (preconditioning effect) or 4 h after IM administration when gastric erosions have been already developed (postconditioning effect). Gastric mucosa was examined for injury 4 h (formation of gastric erosions) and 24 h (healing of gastric erosions) after IM administration. Treadmill was set up horizontally (15 m/min), run was stimulated by shocks 0.2 mA. Control animals were at rest and they were also injected by IM. Corticosterone plasma levels and somatic pain sensitivity (tail flick test) were measured. Forced treadmill running resulted in an increase of tail flick latencies (analgesic effect) which was accompanied by an increase in plasma corticosterone levels. The onset of forced treadmill running 1 h before IM administration increased the plasma corticosterone levels, normalized somatic pain sensitivity and attenuated IM‐induced gastric injury 4 h after IM administration. The onset of forced treadmill running after formation of gastric injury resulted in a decrease of gastric injury 24 h after IM injection comparing with control rats. Thus, forced treadmill running can attenuate gastric injury formation induced by indomethacin (IM) and promote a healing of IM‐induced injury in rats.Support or Funding InformationThe study was supported by grant of Russian Science Foundation (RSF) N 19‐15‐00430.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
In Vitro Studies on the Mechanism of CFTR Inhibition by a Fungus‐derived Compound and Its Potential Anti‐diarrheal Application
Authors: Akrimajirachoote Nattaphong , Satitsri Saravut , Rukachaisirikul Vatcharin , Muanprasat Chatchai 
Published: June 2021

Secretory diarrheas caused by enterotoxin‐producing bacteria are a major global health problem. Overactivation of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channels play an important role in the pathogenesis of secretory diarrheas. Preliminary results in our laboratory found that the fungus‐derived N453 inhibited CFTR‐mediated Cl− secretion with a half maximal inhibitory concentration (IC50) of ̴ 2 μM in intestinal epithelial (T84) cells. This study aimed to explore its underlying mechanisms and to demonstrate its anti‐diarrheal application. As analyzed by apical Cl− current measurement, pretreatment with phosphodiesterase and multi‐drug resistance protein 4 inhibitors did not affect the inhibitory effect of N453 on cAMP‐induced Cl− secretion T84 cells. In addition, N453 inhibited Cl− secretion induced by CPT‐cAMP (non‐hydrolyzable cAMP). These results suggest that CFTR inhibition by N453 does not involve alteration of intracellular cAMP levels. Moreover, N453 inhibited CFTR‐mediated Cl− transport induced by genistein (direct CFTR activator), suggesting that N453 might directly inhibit CFTR activity. Pretreatment with inhibitors of AMP‐activated protein kinase (AMPK) and protein phosphatase (PP), negative regulators of CFTR, did not affect the inhibitory effect of N453 on cAMP‐induced Cl− secretion, suggesting that CFTR inhibition by N453 is not resulted from activation of these negative regulators. Interestingly, N453 inhibited Cl− secretion induced by cholera and heat‐stable enterotoxins. Collectively, N453 derived from fungi acts as CFTR inhibitors, which may be beneficial for the treatment of secretory diarrheas.Support or Funding InformationThis work was supported by the NSTDA Chair Professor grant (the Fourth Grant) of the Crown Property Bureau Foundation, Faculty of Science Mahidol University, Faculty of Graduate Studies Mahidol University and Kasetsart Veterinary Development Funds.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.