17 results on '"Casaburo M"'
Search Results
2. La coscienza del degrado: appunti sulla prevenzione dei danni alle opere d’arte nel XIX secolo in Campania
- Author
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Bensi, Paolo, Casaburo, M, and Galeone, M.
- Published
- 2010
3. Problemi di conservazione e progetti di restauro di dipinti murali in ambienti scavati nella roccia in Campania e in Molise
- Author
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Bensi, Paolo, Casaburo, M., Di Sano, F., and Savastano, M.
- Published
- 2009
4. Aspetti della conservazione dei soffitti lignei delle chiese della Campania
- Author
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Bensi, Paolo, Casaburo, M, and DE ROSA, D.
- Published
- 2009
5. La storia conservativa della pittura murale in Campania attraverso il succedersi degli interventi di restauro del XIX e XX secolo: il caso del chiostro dei Ss.Severino e Sossio a Napoli
- Author
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Bensi, Paolo and Casaburo, M.
- Published
- 2008
6. Reduction of Cardiac Fibrosis by Interference With YAP-Dependent Transactivation
- Author
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Gloria Garoffolo, Manuel Casaburo, Francesco Amadeo, Massimo Salvi, Giacomo Bernava, Luca Piacentini, Isotta Chimenti, Germana Zaccagnini, Gesmi Milcovich, Estella Zuccolo, Marco Agrifoglio, Sara Ragazzini, Otgon Baasansuren, Claudia Cozzolino, Mattia Chiesa, Silvia Ferrari, Dario Carbonaro, Rosaria Santoro, Martina Manzoni, Loredana Casalis, Angela Raucci, Filippo Molinari, Lorenzo Menicanti, Francesca Pagano, Toshiro Ohashi, Fabio Martelli, Diana Massai, Gualtiero I. Colombo, Elisa Messina, Umberto Morbiducci, Maurizio Pesce, Garoffolo G., Casaburo M., Amadeo F., Salvi M., Bernava G., Piacentini L., Chimenti I., Zaccagnini G., Milcovich G., Zuccolo E., Agrifoglio M., Ragazzini S., Baasansuren O., Cozzolino C., Chiesa M., Ferrari S., Carbonaro D., Santoro R., Manzoni M., Casalis L., Raucci A., Molinari F., Menicanti L., Pagano F., Ohashi T., Martelli F., Massai D., Colombo G.I., Messina E., Morbiducci U., and Pesce M.
- Subjects
Transcriptional Activation ,Physiology ,fibrosis ,myofibroblasts ,Verteporfin ,heart failure ,YAP-Signaling Proteins ,Settore MED/11 - Malattie dell'Apparato Cardiovascolare ,Settore MED/23 - Chirurgia Cardiaca ,stromal cell ,transcription factors ,Phosphoproteins ,cell mechanics ,YAP transcription factor ,Mice ,Settore CHIM/09 - Farmaceutico Tecnologico Applicativo ,Trans-Activators ,Animals ,Humans ,Cardiology and Cardiovascular Medicine ,Adaptor Proteins, Signal Transducing - Abstract
Background: Conversion of cardiac stromal cells into myofibroblasts is typically associated with hypoxia conditions, metabolic insults, and/or inflammation, all of which are predisposing factors to cardiac fibrosis and heart failure. We hypothesized that this conversion could be also mediated by response of these cells to mechanical cues through activation of the Hippo transcriptional pathway. The objective of the present study was to assess the role of cellular/nuclear straining forces acting in myofibroblast differentiation of cardiac stromal cells under the control of YAP (yes-associated protein) transcription factor and to validate this finding using a pharmacological agent that interferes with the interactions of the YAP/TAZ (transcriptional coactivator with PDZ-binding motif) complex with their cognate transcription factors TEADs (TEA domain transcription factors), under high-strain and profibrotic stimulation. Methods: We employed high content imaging, 2-dimensional/3-dimensional culture, atomic force microscopy mapping, and molecular methods to prove the role of cell/nuclear straining in YAP-dependent fibrotic programming in a mouse model of ischemia-dependent cardiac fibrosis and in human-derived primitive cardiac stromal cells. We also tested treatment of cells with Verteporfin, a drug known to prevent the association of the YAP/TAZ complex with their cognate transcription factors TEADs. Results: Our experiments suggested that pharmacologically targeting the YAP-dependent pathway overrides the profibrotic activation of cardiac stromal cells by mechanical cues in vitro, and that this occurs even in the presence of profibrotic signaling mediated by TGF-β1 (transforming growth factor beta-1). In vivo administration of Verteporfin in mice with permanent cardiac ischemia reduced significantly fibrosis and morphometric remodeling but did not improve cardiac performance. Conclusions: Our study indicates that preventing molecular translation of mechanical cues in cardiac stromal cells reduces the impact of cardiac maladaptive remodeling with a positive effect on fibrosis.
- Published
- 2022
7. Vascular ageing: the role of oxidative stress
- Author
-
Anna Ferrario, Annibale Alessandro Puca, Francesco Villa, Albino Carrizzo, Anna Maciąg, Manuel Casaburo, Carmine Vecchione, Puca, A, Carrizzo, A, Villa, F, Ferrario, A, Casaburo, M, Macia̧g, A, and Vecchione, C
- Subjects
Aging ,Blood Vessel ,Cellular respiration ,media_common.quotation_subject ,Longevity ,Vascular integrity ,Biology ,medicine.disease_cause ,Biochemistry ,Antioxidants ,chemistry.chemical_compound ,medicine ,Humans ,Endothelial dysfunction ,media_common ,chemistry.chemical_classification ,Reactive oxygen species ,NADPH oxidase ,Cell Biology ,Glutathione ,medicine.disease ,Cell biology ,Ageing ,Oxidative Stress ,chemistry ,Immunology ,biology.protein ,Oxidative stre ,Blood Vessels ,Antioxidant ,Reactive Oxygen Specie ,Reactive Oxygen Species ,Oxidative stress ,Human ,Signal Transduction - Abstract
Vascular ageing can be envisioned as the consequence of the accumulation of reactive oxygen species (ROS) associated with generalized endothelial dysfunction. Oxidative stress arises when the balance between production and removal of ROS favours the pro-oxidation arm. Therefore, ROS have been traditionally considered to be only a toxic by-product of aerobic metabolism. However, it has become apparent that ROS might control many different physiological processes, such as stress response, pathogen defence and systemic signalling. This has lead to the hypothesis that a certain level of ROS is needed physiologically, so much so that an overly increased antioxidant potential might be deleterious for health. Recent evidence has strengthened this notion by correlating cellular response with oxidants and the mechanisms that regulate longevity. Here, we overview current literature on this topic and we will try to convince the reader of the importance of balanced oxidative stress for vascular integrity and healthy ageing. © 2013 Elsevier Ltd.
- Published
- 2012
8. High phosphate-induced JAK-STAT signalling sustains Vascular Smooth Muscle Cells inflammation and limits calcification.
- Author
-
Macrì F, Castiglione S, Faggiano S, Vigorito I, Casaburo M, Fanotti N, Piacentini L, Vigetti D, Vinci MC, and Raucci A
- Subjects
- Animals, Humans, Phosphates metabolism, Janus Kinases metabolism, STAT Transcription Factors metabolism, Inflammation metabolism, Inflammation pathology, Muscle, Smooth, Vascular metabolism, Muscle, Smooth, Vascular pathology, Muscle, Smooth, Vascular drug effects, Signal Transduction, Myocytes, Smooth Muscle metabolism, Myocytes, Smooth Muscle pathology, Myocytes, Smooth Muscle drug effects, Vascular Calcification metabolism, Vascular Calcification pathology
- Published
- 2024
- Full Text
- View/download PDF
9. High Phosphate-Induced JAK-STAT Signalling Sustains Vascular Smooth Muscle Cell Inflammation and Limits Calcification.
- Author
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Macrì F, Vigorito I, Castiglione S, Faggiano S, Casaburo M, Fanotti N, Piacentini L, Vigetti D, Vinci MC, and Raucci A
- Subjects
- Humans, Animals, Mice, Calcium, Janus Kinases, STAT Transcription Factors, Signal Transduction, Inflammation, Muscle, Smooth, Vascular, Vascular Calcification chemically induced
- Abstract
Vascular calcification (VC) is an age-related complication characterised by calcium-phosphate deposition in the arterial wall driven by the osteogenic transformation of vascular smooth muscle cells (VSMCs). The JAK-STAT pathway is an emerging target in inflammation. Considering the relationship between VC and inflammation, we investigated the role of JAK-STAT signalling during VSMC calcification. Human aortic smooth muscle cells (HASMCs) were cultured in high-inorganic phosphate (Pi) medium for up to 7 days; calcium deposition was determined via Alizarin staining and colorimetric assay. Inflammatory factor secretion was evaluated via ELISA and JAK-STAT members' activation using Western blot or immunohistochemistry on HASMCs or calcified aortas of Vitamin D-treated C57BL6/J mice, respectively. The JAK-STAT pathway was blocked by JAK Inhibitor I and Von Kossa staining was used for calcium deposits in murine aortic rings. During Pi-induced calcification, HASMCs released IL-6, IL-8, and MCP-1 and activated JAK1-JAK3 proteins and STAT1. Phospho-STAT1 was detected in murine calcified aortas. Blocking of the JAK-STAT cascade reduced HASMC proliferation and pro-inflammatory factor expression and release while increasing calcium deposition and osteogenic transcription factor RUNX2 expression. Consistently, JAK-STAT pathway inhibition exacerbates mouse aortic ring calcification ex vivo. Intriguingly, our results suggest an alternative link between VSMC inflammation and VC.
- Published
- 2023
- Full Text
- View/download PDF
10. Ischemic wound revascularization by the stromal vascular fraction relies on host-donor hybrid vessels.
- Author
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Vuerich R, Groppa E, Vodret S, Ring NAR, Stocco C, Bossi F, Agostinis C, Cauteruccio M, Colliva A, Ramadan M, Simoncello F, Benvenuti F, Agnelli A, Dore F, Mazzarol F, Moretti M, Paulitti A, Palmisano S, De Manzini N, Chiesa M, Casaburo M, Raucci A, Lorizio D, Pompilio G, Bulla R, Papa G, and Zacchigna S
- Abstract
Nonhealing wounds place a significant burden on both quality of life of affected patients and health systems. Skin substitutes are applied to promote the closure of nonhealing wounds, although their efficacy is limited by inadequate vascularization. The stromal vascular fraction (SVF) from the adipose tissue is a promising therapy to overcome this limitation. Despite a few successful clinical trials, its incorporation in the clinical routine has been hampered by their inconsistent results. All these studies concluded by warranting pre-clinical work aimed at both characterizing the cell types composing the SVF and shedding light on their mechanism of action. Here, we established a model of nonhealing wound, in which we applied the SVF in combination with a clinical-grade skin substitute. We purified the SVF cells from transgenic animals to trace their fate after transplantation and observed that it gave rise to a mature vascular network composed of arteries, capillaries, veins, as well as lymphatics, structurally and functionally connected with the host circulation. Then we moved to a human-in-mouse model and confirmed that SVF-derived endothelial cells formed hybrid human-mouse vessels, that were stabilized by perivascular cells. Mechanistically, SVF-derived endothelial cells engrafted and expanded, directly contributing to the formation of new vessels, while a population of fibro-adipogenic progenitors stimulated the expansion of the host vasculature in a paracrine manner. These data have important clinical implications, as they provide a steppingstone toward the reproducible and effective adoption of the SVF as a standard care for nonhealing wounds., (© 2023. The Author(s).)
- Published
- 2023
- Full Text
- View/download PDF
11. Effects of RAGE Deletion on the Cardiac Transcriptome during Aging.
- Author
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Scavello F, Piacentini L, Castiglione S, Zeni F, Macrì F, Casaburo M, Vinci MC, Colombo GI, and Raucci A
- Subjects
- Animals, Fatty Acids, Female, Fibrosis, Glycation End Products, Advanced genetics, Glycation End Products, Advanced metabolism, Interferon-beta genetics, Mice, Mice, Inbred C57BL, Mice, Knockout, Receptor for Advanced Glycation End Products genetics, Receptor for Advanced Glycation End Products metabolism, Triglycerides, Aging genetics, Aging metabolism, Transcriptome
- Abstract
Cardiac aging is characterized by increased cardiomyocyte hypertrophy, myocardial stiffness, and fibrosis, which enhance cardiovascular risk. The receptor for advanced glycation end-products (RAGE) is involved in several age-related diseases. RAGE knockout ( Rage-/- ) mice show an acceleration of cardiac dimension changes and interstitial fibrosis with aging. This study identifies the age-associated cardiac gene expression signature induced by RAGE deletion. We analyzed the left ventricle transcriptome of 2.5-(Young), 12-(Middle age, MA), and 21-(Old) months-old female Rage-/- and C57BL/6N (WT) mice. By comparing Young, MA, and Old Rage-/- versus age-matched WT mice, we identified 122, 192, and 12 differently expressed genes, respectively. Functional inference analysis showed that RAGE deletion is associated with: (i) down-regulation of genes involved in antigen processing and presentation of exogenous antigen, adaptive immune response, and cellular responses to interferon beta and gamma in Young animals; (ii) up-regulation of genes related to fatty acid oxidation, cardiac structure remodeling and cellular response to hypoxia in MA mice; (iii) up-regulation of few genes belonging to complement activation and triglyceride biosynthetic process in Old animals. Our findings show that the age-dependent cardiac phenotype of Rage-/- mice is associated with alterations of genes related to adaptive immunity and cardiac stress pathways.
- Published
- 2022
- Full Text
- View/download PDF
12. Reduction of Cardiac Fibrosis by Interference With YAP-Dependent Transactivation.
- Author
-
Garoffolo G, Casaburo M, Amadeo F, Salvi M, Bernava G, Piacentini L, Chimenti I, Zaccagnini G, Milcovich G, Zuccolo E, Agrifoglio M, Ragazzini S, Baasansuren O, Cozzolino C, Chiesa M, Ferrari S, Carbonaro D, Santoro R, Manzoni M, Casalis L, Raucci A, Molinari F, Menicanti L, Pagano F, Ohashi T, Martelli F, Massai D, Colombo GI, Messina E, Morbiducci U, and Pesce M
- Subjects
- Animals, Fibrosis, Humans, Mice, Trans-Activators genetics, Trans-Activators metabolism, Transcription Factors genetics, Transcription Factors metabolism, Transcriptional Activation, Verteporfin, YAP-Signaling Proteins, Adaptor Proteins, Signal Transducing metabolism, Phosphoproteins metabolism
- Abstract
Background: Conversion of cardiac stromal cells into myofibroblasts is typically associated with hypoxia conditions, metabolic insults, and/or inflammation, all of which are predisposing factors to cardiac fibrosis and heart failure. We hypothesized that this conversion could be also mediated by response of these cells to mechanical cues through activation of the Hippo transcriptional pathway. The objective of the present study was to assess the role of cellular/nuclear straining forces acting in myofibroblast differentiation of cardiac stromal cells under the control of YAP (yes-associated protein) transcription factor and to validate this finding using a pharmacological agent that interferes with the interactions of the YAP/TAZ (transcriptional coactivator with PDZ-binding motif) complex with their cognate transcription factors TEADs (TEA domain transcription factors), under high-strain and profibrotic stimulation., Methods: We employed high content imaging, 2-dimensional/3-dimensional culture, atomic force microscopy mapping, and molecular methods to prove the role of cell/nuclear straining in YAP-dependent fibrotic programming in a mouse model of ischemia-dependent cardiac fibrosis and in human-derived primitive cardiac stromal cells. We also tested treatment of cells with Verteporfin, a drug known to prevent the association of the YAP/TAZ complex with their cognate transcription factors TEADs., Results: Our experiments suggested that pharmacologically targeting the YAP-dependent pathway overrides the profibrotic activation of cardiac stromal cells by mechanical cues in vitro, and that this occurs even in the presence of profibrotic signaling mediated by TGF-β1 (transforming growth factor beta-1). In vivo administration of Verteporfin in mice with permanent cardiac ischemia reduced significantly fibrosis and morphometric remodeling but did not improve cardiac performance., Conclusions: Our study indicates that preventing molecular translation of mechanical cues in cardiac stromal cells reduces the impact of cardiac maladaptive remodeling with a positive effect on fibrosis.
- Published
- 2022
- Full Text
- View/download PDF
13. Oxidized LDL-dependent pathway as new pathogenic trigger in arrhythmogenic cardiomyopathy.
- Author
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Sommariva E, Stadiotti I, Casella M, Catto V, Dello Russo A, Carbucicchio C, Arnaboldi L, De Metrio S, Milano G, Scopece A, Casaburo M, Andreini D, Mushtaq S, Conte E, Chiesa M, Birchmeier W, Cogliati E, Paolin A, König E, Meraviglia V, De Musso M, Volani C, Cattelan G, Rauhe W, Turnu L, Porro B, Pedrazzini M, Camera M, Corsini A, Tondo C, Rossini A, and Pompilio G
- Subjects
- Animals, Arrhythmias, Cardiac etiology, Humans, Lipoproteins, LDL, Mice, Phenotype, Arrhythmogenic Right Ventricular Dysplasia genetics
- Abstract
Arrhythmogenic cardiomyopathy (ACM) is hallmarked by ventricular fibro-adipogenic alterations, contributing to cardiac dysfunctions and arrhythmias. Although genetically determined (e.g., PKP2 mutations), ACM phenotypes are highly variable. More data on phenotype modulators, clinical prognosticators, and etiological therapies are awaited. We hypothesized that oxidized low-density lipoprotein (oxLDL)-dependent activation of PPARγ, a recognized effector of ACM adipogenesis, contributes to disease pathogenesis. ACM patients showing high plasma concentration of oxLDL display severe clinical phenotypes in terms of fat infiltration, ventricular dysfunction, and major arrhythmic event risk. In ACM patient-derived cardiac cells, we demonstrated that oxLDLs are major cofactors of adipogenesis. Mechanistically, the increased lipid accumulation is mediated by oxLDL cell internalization through CD36, ultimately resulting in PPARγ upregulation. By boosting oxLDL in a Pkp2 heterozygous knock-out mice through high-fat diet feeding, we confirmed in vivo the oxidized lipid dependency of cardiac adipogenesis and right ventricle systolic impairment, which are counteracted by atorvastatin treatment. The modulatory role of oxidized lipids on ACM adipogenesis, demonstrated at cellular, mouse, and patient levels, represents a novel risk stratification tool and a target for ACM pharmacological strategies., (© 2021 The Authors. Published under the terms of the CC BY 4.0 license.)
- Published
- 2021
- Full Text
- View/download PDF
14. Loss of EMILIN-1 Enhances Arteriolar Myogenic Tone Through TGF-β (Transforming Growth Factor-β)-Dependent Transactivation of EGFR (Epidermal Growth Factor Receptor) and Is Relevant for Hypertension in Mice and Humans.
- Author
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Carnevale D, Facchinello N, Iodice D, Bizzotto D, Perrotta M, De Stefani D, Pallante F, Carnevale L, Ricciardi F, Cifelli G, Da Ros F, Casaburo M, Fardella S, Bonaldo P, Innocenzi G, Rizzuto R, Braghetta P, Lembo G, and Bressan GM
- Subjects
- Animals, Blood Pressure, Calcium Channels metabolism, Case-Control Studies, Cells, Cultured, Disease Models, Animal, Female, Heparin-binding EGF-like Growth Factor metabolism, Humans, Hypertension genetics, Hypertension physiopathology, Male, Membrane Glycoproteins deficiency, Membrane Glycoproteins genetics, Mesenteric Arteries drug effects, Mesenteric Arteries physiopathology, Mice, Inbred C57BL, Mice, Knockout, Muscle, Smooth, Vascular metabolism, Muscle, Smooth, Vascular physiopathology, Myocytes, Smooth Muscle metabolism, Signal Transduction, TRPC Cation Channels metabolism, TRPC6 Cation Channel, TRPM Cation Channels metabolism, Transforming Growth Factor beta1 pharmacology, ErbB Receptors metabolism, Hypertension metabolism, Membrane Glycoproteins metabolism, Mesenteric Arteries metabolism, Transforming Growth Factor beta1 metabolism, Vasoconstriction drug effects
- Abstract
Objective- EMILIN-1 (elastin microfibrils interface located protein-1) protein inhibits pro-TGF-β (transforming growth factor-β) proteolysis and limits TGF-β bioavailability in vascular extracellular matrix. Emilin1
-/- null mice display increased vascular TGF-β signaling and are hypertensive. Because EMILIN-1 is expressed in vessels from embryonic life to adulthood, we aimed at unravelling whether the hypertensive phenotype of Emilin1-/- null mice results from a developmental defect or lack of homeostatic role in the adult. Approach and Results- By using a conditional gene targeting inactivating EMILIN-1 in smooth muscle cells of adult mice, we show that increased blood pressure in mice with selective smooth muscle cell ablation of EMILIN-1 depends on enhanced myogenic tone. Mechanistically, we unveil that higher TGF-β signaling in smooth muscle cells stimulates HB-EGF (heparin-binding epidermal growth factor) expression and subsequent transactivation of EGFR (epidermal growth factor receptor). With increasing intraluminal pressure in resistance arteries, the cross talk established by TGF-β and EGFR signals recruits TRPC6 (TRP [transient receptor potential] classical type 6) and TRPM4 (TRP melastatin type 4) channels, lastly stimulating voltage-dependent calcium channels and potentiating myogenic tone. We found reduced EMILIN-1 and enhanced myogenic tone, dependent on increased TGF-β-EGFR signaling, in resistance arteries from hypertensive patients. Conclusions- Taken together, our findings implicate an unexpected role of the TGF-β-EGFR pathway in hypertension with current translational perspectives.- Published
- 2018
- Full Text
- View/download PDF
15. Targeting Interleukin-1β Protects from Aortic Aneurysms Induced by Disrupted Transforming Growth Factor β Signaling.
- Author
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Da Ros F, Carnevale R, Cifelli G, Bizzotto D, Casaburo M, Perrotta M, Carnevale L, Vinciguerra I, Fardella S, Iacobucci R, Bressan GM, Braghetta P, Lembo G, and Carnevale D
- Subjects
- Animals, Cells, Cultured, Chemokine CCL2 antagonists & inhibitors, Interleukin-1beta biosynthesis, Mice, Myocytes, Smooth Muscle immunology, NF-kappa B physiology, Receptors, CCR2 antagonists & inhibitors, Smad4 Protein physiology, Tamoxifen pharmacology, Aortic Aneurysm prevention & control, Interleukin-1beta antagonists & inhibitors, Signal Transduction physiology, Transforming Growth Factor beta physiology
- Abstract
Aortic aneurysms are life-threatening conditions with effective treatments mainly limited to emergency surgery or trans-arterial endovascular stent grafts, thus calling for the identification of specific molecular targets. Genetic studies have highlighted controversial roles of transforming growth factor β (TGF-β) signaling in aneurysm development. Here, we report on aneurysms developing in adult mice after smooth muscle cell (SMC)-specific inactivation of Smad4, an intracellular transducer of TGF-β. The results revealed that Smad4 inhibition activated interleukin-1β (IL-1β) in SMCs. This danger signal later recruited innate immunity in the adventitia through chemokine (C-C motif) ligand 2 (CCL2) and modified the mechanical properties of the aortic wall, thus favoring vessel dilation. SMC-specific Smad4 deletion in Il1r1- or Ccr2-null mice resulted in milder aortic pathology. A chronic treatment with anti-IL-1β antibody effectively hampered aneurysm development. These findings identify a mechanistic target for controlling the progression of aneurysms with compromised TGF-β signaling, such as those driven by SMAD4 mutations., (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Published
- 2017
- Full Text
- View/download PDF
16. Angiotensin (1-7) counteracts the negative effect of angiotensin II on insulin signalling in HUVECs.
- Author
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Tassone EJ, Sciacqua A, Andreozzi F, Presta I, Perticone M, Carnevale D, Casaburo M, Hribal ML, Sesti G, and Perticone F
- Subjects
- Animals, Cells, Cultured, Cyclic GMP metabolism, Cyclic GMP-Dependent Protein Kinases metabolism, Enzyme Activation, Humans, Insulin Receptor Substrate Proteins metabolism, Insulin Resistance, Mesenteric Arteries metabolism, Mice, Nitric Oxide metabolism, Nitric Oxide Synthase Type III metabolism, Phosphatidylinositol 3-Kinase metabolism, Phosphorylation, Proto-Oncogene Mas, Proto-Oncogene Proteins metabolism, Proto-Oncogene Proteins c-akt metabolism, Receptors, G-Protein-Coupled metabolism, Vasodilation, Angiotensin I metabolism, Angiotensin II metabolism, Human Umbilical Vein Endothelial Cells metabolism, Insulin metabolism, Peptide Fragments metabolism, Signal Transduction
- Abstract
Aims: Angiotensin II participates to the regulation of cardiovascular physiology and it is involved in molecular mechanisms of insulin resistance. Angiotensin (1-7), derived from angiotensin II metabolism, is able to counteract many of the haemodynamic and non-haemodynamic actions of angiotensin II. In this study, we investigated in human umbilical vein endothelial cells (HUVECs) the possible action of angiotensin (1-7) on the insulin signalling pathway., Methods and Results: We stimulated HUVECs with insulin, angiotensin II and angiotensin (1-7), testing the effects on endothelial nitric oxide synthase (eNOS) enzyme activation and on insulin receptor substrate-1 (IRS1) phosphorylation. Moreover, we analysed the involvement of angiotensin type1, type2, and Mas receptors in these actions. Finally, we measured the nitric oxide (NO) production, the intracellular cGMP and the PKG-related activity in HUVECs, and the subsequent functional vasoactive effect of angiotensin (1-7) in mesenteric arteries of mice. Angiotensin II inhibits the insulin-induced Akt and eNOS phosphorylation, reducing the NO production. On the other hand, angiotensin (1-7) counteracts the inhibitory effect of angiotensin II, being able to restore the insulin-induced Akt/eNOS activation and the NO production. This effect is mediated by the Mas receptor. The inhibitory effects of angiotensin II on insulin signalling are, at least in part, mediated by an increased serine phosphorylation of IRS₁. Angiotensin (1-7) inhibits the serine phosphorylation of IRS1 induced by angiotensin II., Conclusion: In endothelial cells angiotensin (1-7) counteracts the negative effects of angiotensin II on insulin signalling and NO production. The balance between angiotensin II and angiotensin (1-7) could represent a key mechanism in the pathophysiological processes leading to endothelial dysfunction and insulin-resistance.
- Published
- 2013
- Full Text
- View/download PDF
17. Vascular ageing: the role of oxidative stress.
- Author
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Puca AA, Carrizzo A, Villa F, Ferrario A, Casaburo M, Maciąg A, and Vecchione C
- Subjects
- Aging pathology, Antioxidants metabolism, Blood Vessels metabolism, Blood Vessels pathology, Humans, Longevity physiology, Signal Transduction, Aging physiology, Blood Vessels physiology, Oxidative Stress, Reactive Oxygen Species metabolism
- Abstract
Vascular ageing can be envisioned as the consequence of the accumulation of reactive oxygen species (ROS) associated with generalized endothelial dysfunction. Oxidative stress arises when the balance between production and removal of ROS favours the pro-oxidation arm. Therefore, ROS have been traditionally considered to be only a toxic by-product of aerobic metabolism. However, it has become apparent that ROS might control many different physiological processes, such as stress response, pathogen defence and systemic signalling. This has lead to the hypothesis that a certain level of ROS is needed physiologically, so much so that an overly increased antioxidant potential might be deleterious for health. Recent evidence has strengthened this notion by correlating cellular response with oxidants and the mechanisms that regulate longevity. Here, we overview current literature on this topic and we will try to convince the reader of the importance of balanced oxidative stress for vascular integrity and healthy ageing., (Copyright © 2013 Elsevier Ltd. All rights reserved.)
- Published
- 2013
- Full Text
- View/download PDF
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