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Your search keyword '"Osto, Elena"' showing total 7 results
Start Over Author "Osto, Elena" Topic oxidative stress
7 results on '"Osto, Elena"'

1. Deletion of the activated protein-1 transcription factor JunD induces oxidative stress and accelerates age-related endothelial dysfunction.

Author

Paneni F, Osto E, Costantino S, Mateescu B, Briand S, Coppolino G, Perna E, Mocharla P, Akhmedov A, Kubant R, Rohrer L, Malinski T, Camici GG, Matter CM, Mechta-Grigoriou F, Volpe M, Lüscher TF, and Cosentino F

Subjects
Animals, Endothelium, Vascular metabolism, Homeostasis physiology, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Mitochondria physiology, Models, Animal, Nitric Oxide metabolism, Nitric Oxide Synthase metabolism, Proto-Oncogene Proteins c-jun genetics, Proto-Oncogene Proteins c-jun physiology, Reactive Oxygen Species metabolism, Aging physiology, Endothelium, Vascular physiopathology, Gene Deletion, Oxidative Stress physiology, Proto-Oncogene Proteins c-jun deficiency
Abstract

Background: Reactive oxygen species are major determinants of vascular aging. JunD, a member of the activated protein-1 family of transcription factors, is emerging as a major gatekeeper against oxidative stress. However, its contribution to reactive oxygen species homeostasis in the vasculature remains unknown., Methods and Results: Endothelium-dependent vasorelaxation was impaired in young and old JunD(-/-) mice (6 and 22 months old) compared with age-matched wild-type mice. JunD(-/-) mice displayed an age-independent decline in endothelial nitric oxide release and endothelial nitric oxide synthase activity and increased mitochondrial superoxide formation and peroxynitrite levels. Furthermore, vascular expression and activity of the free radical scavengers manganese and extracellular superoxide dismutase and aldehyde dehydrogenase 2 were reduced, whereas the NADPH oxidase subunits p47phox, Nox2, and Nox4 were upregulated. These redox changes were associated with premature vascular aging, as shown by reduced telomerase activity, increased β-galactosidase-positive cells, upregulation of the senescence markers p16(INK4a) and p53, and mitochondrial disruption. Interestingly, old wild-type mice showed a reduction in JunD expression and transcriptional activity resulting from promoter hypermethylation and binding with tumor suppressor menin, respectively. In contrast, JunD overexpression blunted age-induced endothelial dysfunction. In human endothelial cells, JunD knockdown exerted a similar impairment of the O2(-)/nitric oxide balance that was prevented by concomitant NADPH inhibition. In parallel, JunD expression was reduced in monocytes from old versus young healthy subjects and correlated with mRNA levels of scavenging and oxidant enzymes., Conclusions: JunD provides protection in aging-induced endothelial dysfunction and may represent a novel target to prevent reactive oxygen species-driven vascular aging.

Published
2013
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2. c-Jun N-terminal kinase 2 deficiency protects against hypercholesterolemia-induced endothelial dysfunction and oxidative stress.

Author

Osto E, Matter CM, Kouroedov A, Malinski T, Bachschmid M, Camici GG, Kilic U, Stallmach T, Boren J, Iliceto S, Lüscher TF, and Cosentino F

Subjects
Acetylcholine pharmacology, Animals, Aorta enzymology, Endothelial Cells metabolism, Endothelium, Vascular cytology, Endothelium, Vascular drug effects, Enzyme Activation, Free Radical Scavengers metabolism, Hypercholesterolemia metabolism, JNK Mitogen-Activated Protein Kinases metabolism, Lipids blood, Male, Mice, Mice, Knockout, Mitogen-Activated Protein Kinase 9 metabolism, Nitric Oxide metabolism, Nitric Oxide Synthase Type III metabolism, Vasodilator Agents pharmacology, Endothelium, Vascular physiopathology, Hypercholesterolemia physiopathology, Mitogen-Activated Protein Kinase 9 deficiency, Oxidative Stress, Vasodilation
Abstract

Background: Hypercholesterolemia-induced endothelial dysfunction due to excessive production of reactive oxygen species is a major trigger of atherogenesis. The c-Jun-N-terminal kinases (JNKs) are activated by oxidative stress and play a key role in atherogenesis and inflammation. We investigated whether JNK2 deletion protects from hypercholesterolemia-induced endothelial dysfunction and oxidative stress., Methods and Results: Male JNK2 knockout (JNK2(-/-)) and wild-type (WT) mice (8 weeks old) were fed either a high-cholesterol diet (HCD; 1.25% total cholesterol) or a normal diet for 14 weeks. Aortic lysates of WT mice fed a HCD showed an increase in JNK phosphorylation compared with WT mice fed a normal diet (P<0.05). Endothelium-dependent relaxations to acetylcholine were impaired in WT HCD mice (P<0.05 versus WT normal diet). In contrast, JNK2(-/-) HCD mice did not exhibit endothelial dysfunction (96+/-5% maximal relaxation in response to acetylcholine; P<0.05 versus WT HCD). Endothelium-independent relaxations were identical in all groups. A hypercholesterolemia-induced decrease in nitric oxide (NO) release of endothelial cells was found in WT but not in JNK2(-/-) mice. In parallel, endothelial NO synthase expression was upregulated only in JNK2(-/-) HCD animals, whereas the expression of antioxidant defense systems such as extracellular superoxide dismutase and manganese superoxide dismutase was decreased in WT but not in JNK2(-/-) HCD mice. In contrast to JNK2(-/-) mice, WT HCD displayed an increase in O(2)(-) and ONOO(-) concentrations as well as nitrotyrosine staining and peroxidation., Conclusions: JNK2 plays a critical role as a mediator of hypercholesterolemia-induced endothelial dysfunction and oxidative stress. Thus, JNK2 may provide a novel target for prevention of vascular disease and atherosclerosis.

Published
2008
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3. Pulsatile stretch induces release of angiotensin II and oxidative stress in human endothelial cells: effects of ACE inhibition and AT1 receptor antagonism.

Author

Delli Gatti C, Osto E, Kouroedov A, Eto M, Shaw S, Volpe M, Lüscher TF, and Cosentino F

Subjects
Biomechanical Phenomena, Cells, Cultured, Endothelial Cells metabolism, Hemorheology, Humans, Losartan pharmacology, Models, Biological, Nitric Oxide metabolism, Nitric Oxide Synthase Type III metabolism, Pulsatile Flow, Renin-Angiotensin System drug effects, Renin-Angiotensin System physiology, Stress, Mechanical, Superoxides metabolism, Tetrahydroisoquinolines pharmacology, Angiotensin II metabolism, Angiotensin II Type 1 Receptor Blockers pharmacology, Angiotensin-Converting Enzyme Inhibitors pharmacology, Endothelial Cells drug effects, Endothelial Cells physiology, Oxidative Stress
Abstract

Mechanical forces and the activation of the renin-angiotensin system (RAS) may alter the NO/O2(*-) balance, imparing endothelial nitric oxide (NO) availability. This study investigates the link between RAS and NO/O2(*-) balance in human aortic endothelial cells (HAEC) exposed to pulsatile stretch with and without ACE inhibitor quinaprilat or angiotensin II type 1 (AT(1)) receptor antagonist losartan. Pulsatile stretch increased Ang II levels and O2(*-) production, reducing NO release. RAS blockade with quinaprilat or losartan restored the balance between NO and O2(*-). These results provide a molecular basis for understanding the vascular protective effects of ACE inhibition and AT(1) receptor antagonism.

Published
2008
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6. Inhibition of vascular c-jun N-terminal kinase 2 improves obesity-induced endothelial dysfunction after roux-en-y gastric bypass

Author

Vincenzo Marzolla, Thomas A. Lutz, Thomas Bächler, Simona Stivala, Christian M. Matter, Elena Osto, Lucia Rohrer, Michael Engeli, Petia Doytcheva, Thomas F. Lüscher, Giovanni Pellegrini, Giovanni G. Camici, Francesco Tona, Paul M. Vanhoutte, Erika Tarasco, University of Zurich, and Osto, Elena

Subjects
Male, 0301 basic medicine, obesity, Bariatric surgery, c-Jun N-terminal kinase, Endothelial function, Glucagon-like peptide-1, NO, 030204 cardiovascular system & hematology, Vascular Medicine, 0302 clinical medicine, Phosphorylation, Endothelial dysfunction, Original Research, 10038 Institute of Clinical Chemistry, Kinase, c-jun, 10081 Institute of Veterinary Physiology, Roux-en-Y anastomosis, Vasodilation, Neuroprotective Agents, Cardiovascular Diseases, 10076 Center for Integrative Human Physiology, Endothelium/Vascular Type/Nitric Oxide, 10209 Clinic for Cardiology, c‐Jun N‐terminal kinase, Cardiology and Cardiovascular Medicine, medicine.medical_specialty, Injections, Subcutaneous, Gastric bypass, Gastric Bypass, 10184 Institute of Veterinary Pathology, Pathophysiology, 2705 Cardiology and Cardiovascular Medicine, 03 medical and health sciences, Vascular Biology, Internal medicine, medicine, Animals, Mitogen-Activated Protein Kinase 9, Rats, Wistar, Cardiovascular mortality, glucagon‐like peptide‐1, business.industry, nutritional and metabolic diseases, medicine.disease, Obesity, Rats, Disease Models, Animal, Oxidative Stress, Metabolism, 030104 developmental biology, Endocrinology, 570 Life sciences, biology, Endothelium, Vascular, Peptides, business, Basic Science Research
Abstract

Background Roux‐en‐Y gastric bypass (RYGB) reduces obesity‐associated comorbidities and cardiovascular mortality. RYGB improves endothelial dysfunction, reducing c‐Jun N‐terminal kinase (JNK) vascular phosphorylation. JNK activation links obesity with insulin resistance and endothelial dysfunction. Herein, we examined whether JNK1 or JNK2 mediates obesity‐induced endothelial dysfunction and if pharmacological JNK inhibition can mimic RYGB vascular benefits. Methods and Results After 7 weeks of a high‐fat high‐cholesterol diet, obese rats underwent RYGB or sham surgery; sham–operated ad libitum–fed rats received, for 8 days, either the control peptide D‐TAT or the JNK peptide inhibitor D‐JNKi‐1 (20 mg/kg per day subcutaneous). JNK peptide inhibitor D‐JNKi‐1 treatment improved endothelial vasorelaxation in response to insulin and glucagon‐like peptide‐1, as observed after RYGB. Obesity increased aortic phosphorylation of JNK2, but not of JNK1. RYGB and JNK peptide inhibitor D‐JNKi‐1 treatment blunted aortic JNK2 phosphorylation via activation of glucagon‐like peptide‐1–mediated signaling. The inhibitory phosphorylation of insulin receptor substrate‐1 was reduced, whereas the protein kinase B/endothelial NO synthase pathway was increased and oxidative stress was decreased, resulting in improved vascular NO bioavailability. Conclusions Decreased aortic JNK2 phosphorylation after RYGB rapidly improves obesity‐induced endothelial dysfunction. Pharmacological JNK inhibition mimics the endothelial protective effects of RYGB. These findings highlight the therapeutic potential of novel strategies targeting vascular JNK2 against the severe cardiovascular disease associated with obesity., Journal of the American Heart Association, 6 (11)

Published
2017

7. Rapid and Body Weight Independent Improvement of Endothelial and High-Density Lipoprotein Function After Roux-en-Y Gastric Bypass Role of Glucagon-Like Peptide-1

Author

Marco Bueter, Thomas A. Lutz, Diana Vetter, Kerstin Spliethoff, Petia Doytcheva, François Pattou, Christian M. Matter, Elena Osto, Lucia Rohrer, Caroline Corteville, Francesco Tona, Christian Wolfrum, Reda Hasballa, Anne Tailleux, Helena Buhmann, Thomas F. Lüscher, Paul M. Vanhoutte, Bart Staels, Claudia Dörig, Ulf Landmesser, Jasmin Manz, Sophie Colin, Simona Stivala, University of Zurich, and Osto, Elena

Subjects
Male, medicine.disease_cause, Antioxidants, chemistry.chemical_compound, 2737 Physiology (medical), High-density lipoprotein, Glucagon-Like Peptide 1, Cells, Cultured, 10038 Institute of Clinical Chemistry, 2. Zero hunger, Kinase, 10081 Institute of Veterinary Physiology, Glucagon-like peptide-1, 3. Good health, medicine.anatomical_structure, Treatment Outcome, 10209 Clinic for Cardiology, Female, Cardiology and Cardiovascular Medicine, Lipoproteins, HDL, Signal Transduction, Adult, medicine.medical_specialty, Endothelium, Gastric Bypass, 610 Medicine & health, Diet, High-Fat, Nitric Oxide, 2705 Cardiology and Cardiovascular Medicine, Nitric oxide, Physiology (medical), Internal medicine, Weight Loss, medicine, Animals, Humans, Obesity, Rats, Wistar, Protein kinase B, 10217 Clinic for Visceral and Transplantation Surgery, business.industry, Body Weight, nutritional and metabolic diseases, Rats, Disease Models, Animal, Oxidative Stress, Endocrinology, chemistry, Case-Control Studies, Endothelium, Vascular, business, Proto-Oncogene Proteins c-akt, Oxidative stress, Lipoprotein
Abstract

Background— Roux-en-Y gastric bypass (RYGB) reduces body weight and cardiovascular mortality in morbidly obese patients. Glucagon-like peptide-1 (GLP-1) seems to mediate the metabolic benefits of RYGB partly in a weight loss–independent manner. The present study investigated in rats and patients whether obesity-induced endothelial and high-density lipoprotein (HDL) dysfunction is rapidly improved after RYGB via a GLP-1–dependent mechanism. Methods and Results— Eight days after RYGB in diet-induced obese rats, higher plasma levels of bile acids and GLP-1 were associated with improved endothelium-dependent relaxation compared with sham-operated controls fed ad libitum and sham-operated rats that were weight matched to those undergoing RYGB. Compared with the sham-operated rats, RYGB improved nitric oxide (NO) bioavailability resulting from higher endothelial Akt/NO synthase activation, reduced c-Jun amino terminal kinase phosphorylation, and decreased oxidative stress. The protective effects of RYGB were prevented by the GLP-1 receptor antagonist exendin 9-39 (10 μg·kg −1 ·h −1 ). Furthermore, in patients and rats, RYGB rapidly reversed HDL dysfunction and restored the endothelium-protective properties of the lipoprotein, including endothelial NO synthase activation, NO production, and anti-inflammatory, antiapoptotic, and antioxidant effects. Finally, RYGB restored HDL-mediated cholesterol efflux capacity. To demonstrate the role of increased GLP-1 signaling, sham-operated control rats were treated for 8 days with the GLP-1 analog liraglutide (0.2 mg/kg twice daily), which restored NO bioavailability and improved endothelium-dependent relaxations and HDL endothelium-protective properties, mimicking the effects of RYGB. Conclusions— RYGB rapidly reverses obesity-induced endothelial dysfunction and restores the endothelium-protective properties of HDL via a GLP-1–mediated mechanism. The present translational findings in rats and patients unmask novel, weight-independent mechanisms of cardiovascular protection in morbid obesity.

Published
2015
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