49 results on '"Schiattarella, G. G."'
Search Results
2. Transverse aortic constriction induces gut barrier alterations, microbiota remodeling and systemic inflammation [*Boccella N., Paolillo R. and Coretti L. co-first authors]
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Boccella N., Paolillo R., Coretti L., D'Apice S., Lama A., Giugliano G., Schiattarella G. G., Cuomo M., d'Aquino I., Cavaliere G., Paciello O., Mollica M. P., Mattace Raso G., Esposito G., Lembo F., Perrino C., Boccella, N., Paolillo, R., Coretti, L., D'Apice, S., Lama, A., Giugliano, G., Schiattarella, G. G., Cuomo, M., D'Aquino, I., Cavaliere, G., Paciello, O., Mollica, M. P., Mattace Raso, G., Esposito, G., Lembo, F., and Perrino, C.
- Abstract
Accumulating evidence suggests that modifications of gut function and microbiota composition might play a pivotal role in the pathophysiology of several cardiovascular diseases, including heart failure (HF). In this study we systematically analysed gut microbiota composition, intestinal barrier integrity, intestinal and serum cytokines and serum endotoxin levels in C57BL/6 mice undergoing pressure overload by transverse aortic constriction (TAC) for 1 and 4 weeks. Compared to sham-operated animals, TAC induced prompt and strong weakening of intestinal barrier integrity, long-lasting decrease of colon anti-inflammatory cytokine levels, significant increases of serum levels of bacterial lipopolysaccharide and proinflammatory cytokines. TAC also exerted effects on microbiota composition, inducing significant differences in bacterial genera inside Actinobacteria, Firmicutes, Proteobacteria and TM7 phyla as shown by 16S rDNA sequencing of fecal samples from TAC or sham mice. These results suggest that gut modifications represent an important element to be considered in the development and progression of cardiac dysfunction in response to TAC and support this animal model as a valuable tool to establish the role and mechanisms of gut-heart crosstalk in HF. Evidence arising in this field might identify new treatment options targeting gut integrity and microbiota components to face adverse cardiac events.
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- 2021
3. Small nucleolar RNA SNORD3A: a potential new biomarker and molecular player in heart failure
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Paolillo, R, primary, D'Apice, S, additional, Schiattarella, G G, additional, Holley, C L, additional, Della Corte, A, additional, Bancone, C L, additional, Esposito, G G, additional, and Perrino, C L, additional
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- 2021
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4. P2825Loss of akap1 exacerbates pressure overload-induced cardiac hypertrophy and failure
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Boccella, N, primary, Paolillo, R, additional, Schiattarella, G G, additional, Caputo, E, additional, Pagazzo, V, additional, Cattaneo, F, additional, D'Apice, S, additional, Angilletta, I, additional, Trimarco, B, additional, Esposito, G, additional, and Perrino, C, additional
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- 2018
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5. 4058Effects of selective and nonselective beta-blockers on platelet aggregation in patients with acute coronary syndrome: the PLATE-BLOCK study
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Ilardi, F, primary, Gargiulo, G, additional, Schiattarella, G G, additional, Giugliano, G, additional, Paolillo, R, additional, Menafra, G, additional, De Angelis, E, additional, Franzone, A, additional, Stabile, E, additional, Perrino, C, additional, Cirillo, P, additional, Morisco, C, additional, Izzo, R, additional, Trimarco, V, additional, and Esposito, G, additional
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- 2018
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6. Role of Phosphoinositide 3-kinases and Angiogenesis in Cardiovascular Diseases
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PERRINO, CINZIA, ESPOSITO, GIOVANNI, Gargiulo G., Pironti G., Schiattarella G. G., Chiariello M., Perrino, Cinzia, Esposito, Giovanni, Gargiulo, G., Pironti, G., Schiattarella, G. G., and Chiariello, M.
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- 2011
7. (Zebra) fishing for relevant genes in heart regeneration
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PERRINO, CINZIA, SCHIATTARELLA G. G., Perrino, Cinzia, and Schiattarella, G. G.
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- 2010
8. Biological effects of statins in atherosclerosis
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Franzone A., Schiattarella G. G., Capretti G., Sorrentino S., Pironti G., Sannino A., Chiariello M., PERRINO, CINZIA, ESPOSITO, GIOVANNI, Franzone, A., Schiattarella, G. G., Capretti, G., Sorrentino, S., Pironti, G., Sannino, A., Perrino, Cinzia, Esposito, Giovanni, and Chiariello, M.
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statins - Published
- 2009
9. Statins and the elderly: Recent evidence and current indications
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Schiattarella, G. G., Perrino, C., Magliulo, F., Ilardi, F., Serino, F., Trimarco, V., Izzo, R., Amato, B., Terranova, C., Cardin, F., Militello, C., Leosco, D., Trimarco, B., Giovanni ESPOSITO, Schiattarella, G. G., Perrino, Cinzia, Magliulo, F., Ilardo, F., Serino, F., Trimarco, Valentina, Izzo, Raffaele, Amato, Bruno, Terranova, C., Cardin, F., Militello, C., Leosco, Dario, Trimarco, Bruno, and Esposito, Giovanni
10. The second cAMP messenger and cardiac function regulation: The role of adenylate cyclase | Il secondo messaggero cAMP e la regolazione della funzione cardiaca: Ruolo dell'adenilato ciclasi
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Capretti, G., Anna Franzone, Schiattarella, G. G., Gargiulo, G., Sannino, A., Sorrentino, S., Perrino, C., Esposito, G., and Chiariello, M.
11. New pharmacological strategies for Marfan syndrome: From animal models to humans,Nuove strategie farmacologiche per la sindrome di Marfan: Dai modelli animali all'uomo
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Perrino, C., Schiattarella, G. G., Bottino, R., Fabio Magliulo, Oliveti, M., Esposito, G., and Trimarco, B.
12. New pharmacological strategies for Marfan syndrome: From animal models to humans | Nuove strategie farmacologiche per la sindrome di Marfan: Dai modelli animali all'uomo
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Perrino, C., Schiattarella, G. G., Bottino, R., Magliulo, F., Oliveti, M., Esposito, G., and Bruno Trimarco
13. Novel concepts in β-adrenergic receptor signaling: Therapeutic options for heart failure,Nuovi concetti nella segnalazione β-adrenergica: Prospettive terapeutiche per lo scompenso cardiaco
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Schiattarella, G. G., Perrino, C., Gargiulo, G., Sorrentino, S., Franzone, A., Capretti, G., Giovanni ESPOSITO, and Chiariello, M.
14. Low-dose quinacrine reduces vascular restenosis without affecting re-endothelialization
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Perrino, C., Gargiulo, G., Schiattarella, G. G., Di Serafino, L., Gianluigi Pironti, Magliulo, F., Ilardi, F., Serino, F., Bottino, R., Laurino, F. I., Ferrone, M., Bevilacqua, M., Cirillo, P., Indolfi, C., Trimarco, B., Esposito, G., Perrino, Cinzia, Gargiulo, Giuseppe, Schiattarella, Gabriele Giacomo, Di Serafino, Luigi, Pironti, Gianluigi, Magliulo, Fabio, Ilardi, Federica, Serino, Federica, Bottino, Roberta, Laurino, FLORA ILARIA, Ferrone, Marco, Bevilacqua, Michele, Cirillo, Plinio, Indolfi, Ciro, Trimarco, Bruno, and Esposito, Giovanni
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Physiology ,Physiology (medical) ,Thrombosi ,Smooth muscle cell proliferation ,Drug-eluting stent ,Cardiology and Cardiovascular Medicine ,Re-endothelialization ,In-stent restenosi - Abstract
Background: Coronary drug-eluting stents have significantly reduced the rate of in-stent restenosis, but the rate of in-stent thrombosis seems increased. In this study, we tested whether Quinacrine (Q) might reduce smooth muscle cells (SMC) proliferation while exerting minor effects on endothelial cells proliferation (EC) or thrombosis. Methods: Human SMC and EC were treated with increasing concentrations of Q, and the effects on apoptosis or cell proliferation were tested. Next, we evaluated Q effects on tissue factor (TF) and cell adhesion molecules expression (CAMs) in EC. Finally, we tested Q effects on neointima formation and re-endothelialization in a rat model of carotid artery angioplasty. Results: In SMC, all tested Q concentrations reduced proliferation, increased p53 expression and apoptosis. In contrast, EC, pro-apoptotic effects and TF activation were only observed after prolonged treatment with the highest dose, while CAMs expression was never induced at all concentrations. In vivo, Q induced p53 levels and apoptosis in the neointima, and significantly reduced neointimal formation without affecting re-endothelialization. Conclusion: Q exerts pro-apoptotic effects with higher selectivity for SMC, without pro-thrombotic effects, and might represent a safer drug to prevent or treat artery restenosis after percutaneous interventions.
15. Novel concepts in β-adrenergic receptor signaling: Therapeutic options for heart failure | Nuovi concetti nella segnalazione β-adrenergica: Prospettive terapeutiche per lo scompenso cardiaco
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Schiattarella, G. G., Cinzia Perrino, Gargiulo, G., Sorrentino, S., Franzone, A., Capretti, G., Esposito, G., and Chiariello, M.
16. Heart failure with preserved ejection fraction in humans and mice
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Gabriele G. Schiattarella, Rudolf A. de Boer, Laura M G Meems, Carolyn S.P. Lam, Coenraad Withaar, Withaar, C., Lam, C. S. P., Schiattarella, G. G., De Boer, R. A., and Meems, L. M. G.
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medicine.medical_specialty ,Consensus ,Mouse ,Context (language use) ,Signs and symptoms ,Consensu ,030204 cardiovascular system & hematology ,H2FPEF ,Age and sex ,HFA-PEFF ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Natriuretic Peptide ,Internal medicine ,medicine ,State of the Art Review ,Animals ,Humans ,AcademicSubjects/MED00200 ,Natriuretic Peptides ,Clinical syndrome ,Heart Failure and Cardiomyopathies ,030304 developmental biology ,Heart Failure ,0303 health sciences ,Ejection fraction ,business.industry ,Animal ,Multifactorial disease ,Translational ,Stroke Volume ,medicine.disease ,HFpEF ,3. Good health ,Algorithm ,Heart failure ,Cardiology ,Cardiology and Cardiovascular Medicine ,business ,Heart failure with preserved ejection fraction ,Algorithms ,Human - Abstract
Heart failure (HF) with preserved ejection fraction (HFpEF) is a multifactorial disease accounting for a large and increasing proportion of all clinical HF presentations. As a clinical syndrome, HFpEF is characterized by typical signs and symptoms of HF, a distinct cardiac phenotype and raised natriuretic peptides. Non-cardiac comorbidities frequently co-exist and contribute to the pathophysiology of HFpEF. To date, no therapy has proven to improve outcomes in HFpEF, with drug development hampered, at least partly, by lack of consensus on appropriate standards for pre-clinical HFpEF models. Recently, two clinical algorithms (HFA-PEFF and H2FPEF scores) have been developed to improve and standardize the diagnosis of HFpEF. In this review, we evaluate the translational utility of HFpEF mouse models in the context of these HFpEF scores. We systematically recorded evidence of symptoms and signs of HF or clinical HFpEF features and included several cardiac and extra-cardiac parameters as well as age and sex for each HFpEF mouse model. We found that most of the pre-clinical HFpEF models do not meet the HFpEF clinical criteria, although some multifactorial models resemble human HFpEF to a reasonable extent. We therefore conclude that to optimize the translational value of mouse models to human HFpEF, a novel approach for the development of pre-clinical HFpEF models is needed, taking into account the complex HFpEF pathophysiology in humans., Graphical Abstract An in-depth review of existing pre-clinical HFpEF mouse models with validation of their translational value using the HFA-PEFF and H2FPEF scores.
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- 2021
17. Xbp1s-FoxO1 axis governs lipid accumulation and contractile performance in heart failure with preserved ejection fraction
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Joseph A. Hill, Xuliang Wang, Nan Jiang, Soo Young Kim, Stephen B. Spurgin, Hande Piristine, Sergio Lavandero, Kristin M. French, Vlad G. Zaha, Francisco Altamirano, Subhajit Dasgupta, Anwarul Ferdous, Theodore M. Hill, Herman I. May, Thomas G. Gillette, Maayan Waldman, Dan Tong, Gabriele G. Schiattarella, Heesoo Yoo, Yuxuan Luo, Elisa Villalobos, Schiattarella, G. G., Altamirano, F., Kim, S. Y., Tong, D., Ferdous, A., Piristine, H., Dasgupta, S., Wang, X., French, K. M., Villalobos, E., Spurgin, S. B., Waldman, M., Jiang, N., May, H. I., Hill, T. M., Luo, Y., Yoo, H., Zaha, V. G., Lavandero, S., Gillette, T. G., and Hill, J. A.
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0301 basic medicine ,X-Box Binding Protein 1 ,Ubiquitin-Protein Ligase ,Transcription, Genetic ,General Physics and Astronomy ,FOXO1 ,030204 cardiovascular system & hematology ,Heart Ventricle ,Mice ,0302 clinical medicine ,Ubiquitin ,HEK293 Cell ,Myocytes, Cardiac ,Proteolysi ,Conserved Sequence ,Multidisciplinary ,biology ,Chemistry ,Forkhead Box Protein O1 ,Protein Stability ,Cell biology ,Ubiquitin ligase ,Phenotype ,Cell signalling ,Human ,Heart Ventricles ,Ubiquitin-Protein Ligases ,Science ,Models, Biological ,Article ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,medicine ,Animals ,Humans ,Transcription factor ,STUB1 ,Heart Failure ,Binding Sites ,Base Sequence ,Animal ,Myocardium ,Binding Site ,Stroke Volume ,General Chemistry ,medicine.disease ,Lipid Metabolism ,Myocardial Contraction ,Mice, Inbred C57BL ,HEK293 Cells ,030104 developmental biology ,Cardiovascular and Metabolic Diseases ,Heart failure ,Proteolysis ,biology.protein ,Unfolded protein response ,Heart failure with preserved ejection fraction ,Gene Deletion - Abstract
Heart failure with preserved ejection fraction (HFpEF) is now the dominant form of heart failure and one for which no efficacious therapies exist. Obesity and lipid mishandling greatly contribute to HFpEF. However, molecular mechanism(s) governing metabolic alterations and perturbations in lipid homeostasis in HFpEF are largely unknown. Here, we report that cardiomyocyte steatosis in HFpEF is coupled with increases in the activity of the transcription factor FoxO1 (Forkhead box protein O1). FoxO1 depletion, as well as over-expression of the Xbp1s (spliced form of the X-box-binding protein 1) arm of the UPR (unfolded protein response) in cardiomyocytes each ameliorates the HFpEF phenotype in mice and reduces myocardial lipid accumulation. Mechanistically, forced expression of Xbp1s in cardiomyocytes triggers ubiquitination and proteasomal degradation of FoxO1 which occurs, in large part, through activation of the E3 ubiquitin ligase STUB1 (STIP1 homology and U-box-containing protein 1) a novel and direct transcriptional target of Xbp1s. Our findings uncover the Xbp1s-FoxO1 axis as a pivotal mechanism in the pathogenesis of cardiometabolic HFpEF and unveil previously unrecognized mechanisms whereby the UPR governs metabolic alterations in cardiomyocytes., Heart failure with preserved ejection fraction (HFpEF) is a global, major health issue for which no effective therapies are available. Here, the authors discover that the interplay between two transcription factors, Xbp1s and FoxO1, is critical for metabolic adaptation and lipid handling in HFpEF-stressed cardiomyocytes.
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- 2021
18. Immunoglobulins G modulate endothelial function and affect insulin sensitivity in humans
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Raffaele Napoli, Antonio Ruvolo, Fabio Magliulo, Cecilia Nigro, Claudia Miele, Giuseppe Spadaro, Antonio Pecoraro, Antonio Cittadini, Giovanni Esposito, Paola Triggianese, Simona Grassi, Gabriele G. Schiattarella, Amato de Paulis, Nella Prevete, Napoli, R., Ruvolo, A., Triggianese, P., Prevete, N., Schiattarella, G. G., Nigro, C., Miele, C., Magliulo, F., Grassi, S., Pecoraro, A., Cittadini, A., Esposito, G., de Paulis, A., and Spadaro, G.
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Blood Glucose ,Male ,Time Factors ,Brachial Artery ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Medicine (miscellaneous) ,chemistry.chemical_compound ,Insulin ,Medicine ,Infusions, Intravenou ,Brachial artery ,Endothelial dysfunction ,Infusions, Intravenous ,Cells, Cultured ,Nutrition and Dietetics ,biology ,Flow mediated dilation ,Immunoglobulins, Intravenous ,Vasodilation ,Treatment Outcome ,Atherosclerosi ,Female ,Antibody ,Case-Control Studie ,Cardiology and Cardiovascular Medicine ,Human ,medicine.medical_specialty ,Time Factor ,Adolescent ,Nitric Oxide ,Nitric oxide ,Young Adult ,Insulin resistance ,Internal medicine ,Diabetes mellitus ,medicine.artery ,Immunoglobulin ,Humans ,business.industry ,Common variable immunodeficiency ,Endothelial function ,Biomarker ,medicine.disease ,Common Variable Immunodeficiency ,Endocrinology ,chemistry ,Immunoglobulins, Intravenou ,Case-Control Studies ,Immunoglobulin G ,biology.protein ,Endothelium, Vascular ,Insulin Resistance ,business ,Biomarkers - Abstract
Background and aims: Data from animals suggest that immunoglobulins G (IgG) play a mechanistic role in atherosclerosis and diabetes through endothelial dysfunction and insulin resistance. Patients with common variable immunodeficiency (CVID), who have low circulating levels of IgG and are treated with intravenous polyclonal IgG (IVIgG), may provide an ideal model to clarify whether circulating IgG modulate endothelial function and affect insulin sensitivity in humans. Methods and results: We studied 24 patients with CVID and 17 matched healthy controls (HC). Endothelial function was evaluated as flow mediated dilation (FMD) of the brachial artery at baseline and 1, 7, 14, and 21 days after IVIgG infusion in the CVID patients. We measured also plasma glucose, insulin, and calculated the HOMA-IR index. We also investigated the role of human IgG on the production of Nitric Oxide (NO) in vitro in Human Coronary Artery Endothelial Cells (HCAEC). Compared to HC, FMD of CVID patients was significantly impaired at baseline (9.4 ± 0.9 and 7.6 ± 0.6% respectively, p < 0.05) but rose above normal levels 1 and 7 days after IVIgG infusion to return at baseline at 14 and 21 days. Serum insulin concentration and HOMA-IR index dropped by 50% in CVID patients after IVIgG (p < 0.002 vs. baseline). In vitro IgG stimulated NO production in HCAEC. Conclusions: Reduced IgG levels are associated with endothelial dysfunction and IVIgG stimulates endothelial function directly while improving insulin sensitivity. The current findings may suggest an anti-atherogenic role of human IgG.
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- 2020
19. Remodeling of substrate consumption in the murine sTAC model of heart failure
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Matthew E. Merritt, Aslan T. Turer, Francisco Altamirano, Craig R. Malloy, Herman I. May, Thomas G. Gillette, Gabriele G. Schiattarella, Turer, A., Altamirano, F., Schiattarella, G. G., May, H., Gillette, T. G., Malloy, C. R., and Merritt, M. E.
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Male ,0301 basic medicine ,Pyruvate decarboxylation ,Citric Acid Cycle ,Metabolomic ,Oxidative phosphorylation ,030204 cardiovascular system & hematology ,Article ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Acetyl Coenzyme A ,Pyruvic Acid ,medicine ,Animals ,Metabolomics ,Glycolysis ,Molecular Biology ,Aorta ,Heart Failure ,chemistry.chemical_classification ,Animal ,Myocardium ,Fatty acid ,Substrate selection ,Heart ,medicine.disease ,Ketone ,Constriction ,Hypertensive heart disease ,Mice, Inbred C57BL ,Citric acid cycle ,Disease Models, Animal ,Glucose ,030104 developmental biology ,chemistry ,Biochemistry ,Anaplerosi ,Heart failure ,Metabolome ,Energy Metabolism ,Cardiology and Cardiovascular Medicine ,Energy source ,Oxidation-Reduction - Abstract
Background Energy metabolism and substrate selection are key aspects of correct myocardial mechanical function. Myocardial preference for oxidizable substrates changes in both hypertrophy and in overt failure. Previous work has shown that glucose oxidation is upregulated in overpressure hypertrophy, but its fate in overt failure is less clear. Anaplerotic flux of pyruvate into the tricarboxylic acid cycle (TCA) has been posited as a secondary fate of glycolysis, aside from pyruvate oxidation or lactate production. Methods and results A model of heart failure that emulates both valvular and hypertensive heart disease, the severe transaortic constriction (sTAC) mouse, was assayed for changes in substrate preference using metabolomic and carbon-13 flux measurements. Quantitative measures of O2 consumption in the Langendorff perfused mouse heart were paired with 13C isotopomer analysis to assess TCA cycle turnover. Since the heart accommodates oxidation of all physiological energy sources, the utilization of carbohydrates, fatty acids, and ketones were measured simultaneously using a triple-tracer NMR method. The fractional contribution of glucose to acetyl-CoA production was upregulated in heart failure, while other sources were not significantly different. A model that includes both pyruvate carboxylation and anaplerosis through succinyl-CoA produced superior fits to the data compared to a model using only pyruvate carboxylation. In the sTAC heart, anaplerosis through succinyl-CoA is elevated, while pyruvate carboxylation was not. Metabolomic data showed depleted TCA cycle intermediate pool sizes versus the control, in agreement with previous results. Conclusion In the sTAC heart failure model, the glucose contribution to acetyl-CoA production was significantly higher, with compensatory changes in fatty acid and ketone oxidation not reaching a significant level. Anaplerosis through succinyl-CoA is also upregulated, and is likely used to preserve TCA cycle intermediate pool sizes. The triple tracer method used here is new, and can be used to assess sources of acetyl-CoA production in any oxidative tissue.
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- 2019
20. Nitrosative stress drives heart failure with preserved ejection fraction
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Nan Jiang, Sergio Lavandero, Kristin M. French, Thomas G. Gillette, Kavita Sharma, Virginia S. Hahn, Gabriele G. Schiattarella, David A. Kass, Dong I. Lee, Dan Tong, Soo Young Kim, Zhao V. Wang, Elisa Villalobos, Xiang Luo, Joseph A. Hill, Jian Huang, Francisco Altamirano, Pradeep P.A. Mammen, Theodore M. Hill, Herman I. May, Schiattarella, G. G., Altamirano, F., Tong, D., French, K. M., Villalobos, E., Kim, S. Y., Luo, X., Jiang, N., May, H. I., Wang, Z. V., Hill, T. M., Mammen, P. P. A., Huang, J., Lee, D. I., Hahn, V. S., Sharma, K., Kass, D. A., Lavandero, S., Gillette, T. G., and Hill, J. A.
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Male ,X-Box Binding Protein 1 ,0301 basic medicine ,medicine.medical_specialty ,XBP1 ,Protein Serine-Threonine Kinase ,Nitrosative Stre ,Nitric Oxide Synthase Type II ,030204 cardiovascular system & hematology ,Diet, High-Fat ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Myocyte ,Myocytes, Cardiac ,Endoribonuclease ,Heart Failure ,Multidisciplinary ,Ejection fraction ,biology ,Animal ,business.industry ,Stroke Volume ,Stroke volume ,Mice, Inbred C57BL ,Nitric oxide synthase ,Disease Models, Animal ,NG-Nitroarginine Methyl Ester ,Phenotype ,030104 developmental biology ,Endocrinology ,biology.protein ,Unfolded protein response ,Signal transduction ,business ,Heart failure with preserved ejection fraction ,Human ,Signal Transduction - Abstract
Heart failure with preserved ejection fraction (HFpEF) is a common syndrome with high morbidity and mortality for which there are no evidence-based therapies. Here we report that concomitant metabolic and hypertensive stress in mice—elicited by a combination of high-fat diet and inhibition of constitutive nitric oxide synthase using Nω-nitro-l-arginine methyl ester (l-NAME)—recapitulates the numerous systemic and cardiovascular features of HFpEF in humans. Expression of one of the unfolded protein response effectors, the spliced form of X-box-binding protein 1 (XBP1s), was reduced in the myocardium of our rodent model and in humans with HFpEF. Mechanistically, the decrease in XBP1s resulted from increased activity of inducible nitric oxide synthase (iNOS) and S-nitrosylation of the endonuclease inositol-requiring protein 1α (IRE1α), culminating in defective XBP1 splicing. Pharmacological or genetic suppression of iNOS, or cardiomyocyte-restricted overexpression of XBP1s, each ameliorated the HFpEF phenotype. We report that iNOS-driven dysregulation of the IRE1α–XBP1 pathway is a crucial mechanism of cardiomyocyte dysfunction in HFpEF. iNOS-driven dysregulation of the IRE1α–XBP1 pathway leads to cardiomyocyte dysfunction in mice and recapitulates the systemic and cardiovascular features of human heart failure with preserved ejection fraction.
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- 2019
21. Metabolism and Inflammation in Cardiovascular Health and Diseases: Mechanisms to Therapies
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Gabriele G. Schiattarella, Joseph A. Hill, Rong Tian, Yibin Wang, Schiattarella, G. G., Wang, Y., Tian, R., and Hill, J. A.
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business.industry ,Animal ,Cardiovascular health ,MEDLINE ,Disease Management ,Inflammation ,Bioinformatics ,Cardiovascular System ,Article ,Cardiovascular Physiological Phenomena ,Cardiovascular Diseases ,Cardiovascular Disease ,medicine ,Animals ,Humans ,Disease Susceptibility ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,Energy Metabolism ,Molecular Biology ,Human - Published
- 2021
22. NAD+Repletion Reverses Heart Failure with Preserved Ejection Fraction
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Sergio Lavandero, Pamela A. Szweda, Joseph A. Hill, Luke I. Szweda, Heesoo Yoo, Abdallah Elnwasany, Francisco Altamirano, Gabriele G. Schiattarella, Nan Jiang, Dong I. Lee, Dan Tong, David A. Kass, Eric Verdin, Thomas G. Gillette, Tong, D., Schiattarella, G. G., Jiang, N., Altamirano, F., Szweda, P. A., Elnwasany, A., Lee, D. I., Yoo, H., Kass, D. A., Szweda, L. I., Lavandero, S., Verdin, E., Gillette, T. G., and Hill, J. A.
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0301 basic medicine ,Male ,Niacinamide ,medicine.medical_specialty ,Physiology ,Cardiomyopathy ,heart failure ,Down-Regulation ,030204 cardiovascular system & hematology ,Ketone Oxidoreductase ,Acyl-CoA Dehydrogenase ,Mitochondria, Heart ,03 medical and health sciences ,Mice ,Pyridinium Compound ,0302 clinical medicine ,Mitochondrial Myopathie ,Oxygen Consumption ,Internal medicine ,Sirtuin 3 ,medicine ,Heart Failure, Diastolic ,Chemistry ,Animal ,Acetylation ,medicine.disease ,NAD ,mitochondria ,Mice, Inbred C57BL ,Disease Models, Animal ,030104 developmental biology ,Heart failure ,Cardiology ,NAD+ kinase ,Cardiology and Cardiovascular Medicine ,Heart failure with preserved ejection fraction ,cardiomyopathy ,Oxidation-Reduction ,Fatty Acid ,Human - Abstract
Rationale: Heart failure with preserved ejection fraction (HFpEF) is a mortal clinical syndrome without effective therapies. We recently demonstrated in mice that a combination of metabolic and hypertensive stress recapitulates key features of human HFpEF. Objective: Using this novel preclinical HFpEF model, we set out to define and manipulate metabolic dysregulations occurring in HFpEF myocardium. Methods and Results: We observed impairment in mitochondrial fatty acid oxidation associated with hyperacetylation of key enzymes in the pathway. Downregulation of sirtuin 3 and deficiency of NAD + secondary to an impaired NAD + salvage pathway contribute to this mitochondrial protein hyperacetylation. Impaired expression of genes involved in NAD + biosynthesis was confirmed in cardiac tissue from patients with HFpEF. Supplementing HFpEF mice with nicotinamide riboside or a direct activator of NAD + biosynthesis led to improvement in mitochondrial function and amelioration of the HFpEF phenotype. Conclusions: Collectively, these studies demonstrate that HFpEF is associated with myocardial mitochondrial dysfunction and unveil NAD + repletion as a promising therapeutic approach in the syndrome.
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- 2021
23. Metabolic inflammation in heart failure with preserved ejection fraction
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Joseph A. Hill, Daniele Rodolico, Gabriele G. Schiattarella, Schiattarella, G. G., Rodolico, D., and Hill, J. A.
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Adult ,Male ,Metabolic inflammation ,Physiology ,Anti-Inflammatory Agents ,Reviews ,Cardiac metabolism ,Inflammation ,Disease ,Comorbidity ,Bioinformatics ,Ventricular Function, Left ,Pathogenesis ,Immunity ,Physiology (medical) ,medicine ,Humans ,Obesity ,Inflammation Mediator ,Heart Failure ,business.industry ,Myocardium ,Stroke Volume ,HFpEF ,Pathophysiology ,Anti-Inflammatory Agent ,Metabolism ,Female ,Inflammation Mediators ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,Heart failure with preserved ejection fraction ,business ,Energy Metabolism ,Human ,Signal Transduction - Abstract
One in 10 persons in the world aged 40 years and older will develop the syndrome of HFpEF (heart failure with preserved ejection fraction), the most common form of chronic cardiovascular disease for which no effective therapies are currently available. Metabolic disturbance and inflammatory burden contribute importantly to HFpEF pathogenesis. The interplay within these two biological processes is complex; indeed, it is now becoming clear that the notion of metabolic inflammation—metainflammation—must be considered central to HFpEF pathophysiology. Inflammation and metabolism interact over the course of syndrome progression, and likely impact HFpEF treatment and prevention. Here, we discuss evidence in support of a causal, mechanistic role of metainflammation in shaping HFpEF, proposing a framework in which metabolic comorbidities profoundly impact cardiac metabolism and inflammatory pathways in the syndrome.
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- 2021
24. Epigenetic Reader BRD4 (Bromodomain-Containing Protein 4) Governs Nucleus-Encoded Mitochondrial Transcriptome to Regulate Cardiac Function
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Gabriele G. Schiattarella, Thaís A. R. Ramos, Soo Young Kim, Sergio Lavandero, Kristin M. French, Xin Zhang, Luke I. Szweda, Hongliang Li, Vinicius Maracaja-Coutinho, Herman I. May, Thomas G. Gillette, Xiang Luo, Pamela A. Szweda, Francisco Altamirano, Bret M. Evers, Joseph A. Hill, Nan Jiang, Kim, S. Y., Zhang, X., Schiattarella, G. G., Altamirano, F., Ramos, T. A. R., French, K. M., Jiang, N., Szweda, P. A., Evers, B. M., May, H. I., Luo, X., Li, H., Szweda, L. I., Maracaja-Coutinho, V., Lavandero, S., Gillette, T. G., and Hill, J. A.
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Cardiac function curve ,Cardiomyopathy, Dilated ,BRD4 ,transcription, genetic ,Transcription Factor ,Mitochondrion ,Mitochondria, Heart ,Ventricular Function, Left ,Article ,Epigenesis, Genetic ,Transcriptome ,03 medical and health sciences ,Ventricular Dysfunction, Left ,0302 clinical medicine ,Transcription (biology) ,Physiology (medical) ,Medicine ,Animals ,Myocytes, Cardiac ,electron transport ,Epigenetics ,Cell Nucleu ,Nuclear Protein ,030304 developmental biology ,Cell Nucleus ,Heart Failure ,Mice, Knockout ,0303 health sciences ,Electron Transport Chain Complex Protein ,Animal ,business.industry ,Gene Expression Profiling ,Estrogen Receptor alpha ,Nuclear Proteins ,BRD4 protein, human ,Cell biology ,Bromodomain ,mitochondria ,medicine.anatomical_structure ,Electron Transport Chain Complex Proteins ,Cardiology and Cardiovascular Medicine ,business ,Energy Metabolism ,Nucleus ,epigenetic ,030217 neurology & neurosurgery ,Transcription Factors - Abstract
Background: BET (bromodomain and extraterminal) epigenetic reader proteins, in particular BRD4 (bromodomain-containing protein 4), have emerged as potential therapeutic targets in a number of pathological conditions, including cancer and cardiovascular disease. Small-molecule BET protein inhibitors such as JQ1 have demonstrated efficacy in reversing cardiac hypertrophy and heart failure in preclinical models. Yet, genetic studies elucidating the biology of BET proteins in the heart have not been conducted to validate pharmacological findings and to unveil potential pharmacological side effects. Methods: By engineering a cardiomyocyte-specific BRD4 knockout mouse, we investigated the role of BRD4 in cardiac pathophysiology. We performed functional, transcriptomic, and mitochondrial analyses to evaluate BRD4 function in developing and mature hearts. Results: Unlike pharmacological inhibition, loss of BRD4 protein triggered progressive declines in myocardial function, culminating in dilated cardiomyopathy. Transcriptome analysis of BRD4 knockout mouse heart tissue identified early and specific disruption of genes essential to mitochondrial energy production and homeostasis. Functional analysis of isolated mitochondria from these hearts confirmed that BRD4 ablation triggered significant changes in mitochondrial electron transport chain protein expression and activity. Computational analysis identified candidate transcription factors participating in the BRD4-regulated transcriptome. In particular, estrogen-related receptor α, a key nuclear receptor in metabolic gene regulation, was enriched in promoters of BRD4-regulated mitochondrial genes. Conclusions: In aggregate, we describe a previously unrecognized role for BRD4 in regulating cardiomyocyte mitochondrial homeostasis, observing that its function is indispensable to the maintenance of normal cardiac function.
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- 2020
25. Impact of chronic kidney disease on platelet aggregation in patients with acute coronary syndrome
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Gabriele G. Schiattarella, Sara Cimino, Carmine Morisco, Giuseppe Giugliano, Nicola Verde, Giuseppe Gargiulo, Enrico Coscioni, Giovanni Esposito, Eugenio Stabile, Roberta Paolillo, Marco Ferrone, Cinzia Perrino, Plinio Cirillo, Federica Ilardi, Ilardi, F., Gargiulo, G., Paolillo, R., Ferrone, M., Cimino, S., Giugliano, G., Schiattarella, G. G., Verde, N., Stabile, E., Perrino, C., Cirillo, P., Coscioni, E., Morisco, C., and Esposito, G.
- Subjects
Male ,medicine.medical_specialty ,Acute coronary syndrome ,Ticagrelor ,Platelet Aggregation ,Platelet Function Tests ,Drug Resistance ,Renal function ,Kidney ,Gastroenterology ,Risk Assessment ,Severity of Illness Index ,Coronary artery disease ,P2Y12 ,Percutaneous Coronary Intervention ,Risk Factors ,Internal medicine ,medicine ,Humans ,Platelet ,Acute Coronary Syndrome ,Renal Insufficiency, Chronic ,Aged ,Aspirin ,business.industry ,Dual Anti-Platelet Therapy ,General Medicine ,Odds ratio ,Middle Aged ,medicine.disease ,Clopidogrel ,Treatment Outcome ,Purinergic P2Y Receptor Antagonists ,Female ,Cardiology and Cardiovascular Medicine ,business ,Prasugrel Hydrochloride ,Platelet Aggregation Inhibitors ,medicine.drug ,Kidney disease ,Glomerular Filtration Rate - Abstract
AIMS: Chronic kidney disease (CKD) is associated with increased thrombotic events and seems to influence platelet reactivity. Conflicting results have been published on platelet response in CKD patients with stable coronary artery disease. The aim of our study was to investigate the impact of CKD on platelet aggregation in acute coronary syndrome (ACS) patients receiving dual antiplatelet therapy, included the more potent P2Y12 inhibitors. METHODS: We enrolled 206 patients with ACS, divided in two groups, according to the presence or the absence of moderate/severe CKD. Platelet aggregation was performed with light transmission aggregometry and results are expressed as percentage of maximum platelet aggregation. High residual platelet reactivity (HRPR) was defined as maximum platelet aggregation more than 59%. RESULTS: Patients with CKD [estimate glomerular filtration rate (eGFR)
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- 2020
26. The role of mitochondrial dynamics in cardiovascular diseases
- Author
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Sebastiano Sciarretta, Gabriele G. Schiattarella, Leonardo Schirone, Lia Crotti, Cinzia Perrino, Daniele Catalucci, Ciro Indolfi, Jessica Modica, Maurizio Forte, Daniele Torella, Speranza Rubattu, Cristina Basso, Cristina Chimenti, Giacomo Frati, Pietro Ameri, Forte, M, Schirone, L, Ameri, P, Basso, C, Catalucci, D, Modica, J, Chimenti, C, Crotti, L, Frati, G, Rubattu, S, Schiattarella, G, Torella, D, Perrino, C, Indolfi, C, Sciarretta, S, Forte, M., Schirone, L., Ameri, P., Basso, C., Catalucci, D., Modica, J., Chimenti, C., Crotti, L., Frati, G., Rubattu, S., Schiattarella, G. G., Torella, D., Perrino, C., Indolfi, C., and Sciarretta, S.
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0301 basic medicine ,Ischemia ,Disease ,Mitochondrion ,Mitochondrial Dynamics ,Brain Ischemia ,03 medical and health sciences ,0302 clinical medicine ,cardiovascular disease ,medicine ,Humans ,Pharmacology ,Pressure overload ,BIO/15 - BIOLOGIA FARMACEUTICA ,mitochondria ,mitochondrial dynamics ,fission ,fusion ,cardiovascular ,heart ,myocardium ,myocardial ,drp1 ,mfn1 ,mfn2 ,opa1 ,business.industry ,Myocardium ,MED/11 - MALATTIE DELL'APPARATO CARDIOVASCOLARE ,medicine.disease ,Pathophysiology ,Stroke ,030104 developmental biology ,Cardiovascular Diseases ,Heart failure ,business ,Reperfusion injury ,Neuroscience ,030217 neurology & neurosurgery ,Biogenesis - Abstract
The process of mitochondrial dynamics is emerging as a core player in cardiovascular homeostasis. This process refers to the co-ordinated cycles of biogenesis, fusion, fission and degradation to which mitochondria constantly undergo to maintain their integrity, distribution and size. These mechanisms represent an early response to mitochondrial stress, confining organelle portions that are irreversibly damaged and preserving mitochondrial function. Accumulating evidence demonstrates that impairment in mitochondrial dynamics leads to myocardial damage and cardiac disease progression in a variety of disease models, including pressure overload, ischaemia/reperfusion and metabolic disturbance. These findings suggest that modulation of mitochondrial dynamics may be considered as a valid therapeutic strategy in cardiovascular diseases. In this review, we discuss the current evidence about the role of mitochondrial dynamics in cardiac pathophysiology, with a particular focus on the mechanisms underlying the development of cardiac hypertrophy and heart failure, metabolic and genetic cardiomyopathies, ischaemia/reperfusion injury, atherosclerosis and ischaemic stroke. LINKED ARTICLES: This article is part of a themed issue on Cellular metabolism and diseases. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.10/issuetoc.
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- 2020
27. Distinctive patterns of inflammation across the heart failure syndrome
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Pietro Ameri, Gabriele G. Schiattarella, Vasco Sequeira, Schiattarella, G. G., Sequeira, V., and Ameri, P.
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Prognosi ,Inflammation ,Pathogenesis ,030204 cardiovascular system & hematology ,Bioinformatics ,Ventricular Function, Left ,Comorbidities ,03 medical and health sciences ,Ventricular Dysfunction, Left ,0302 clinical medicine ,Pathogenesi ,medicine ,Humans ,In patient ,030212 general & internal medicine ,Myocardial infarction ,Cytokines ,Heart failure ,Cytokine ,Heart Failure ,Ejection fraction ,business.industry ,Cancer ,Stroke Volume ,medicine.disease ,Prognosis ,Comorbiditie ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,Human ,Kidney disease - Abstract
Inflammation has long been known to play a role in heart failure (HF). Earlier studies demonstrated that inflammation contributes to the pathogenesis of HF with reduced ejection fraction (HFrEF), and the knowledge about molecules and cell types specifically involved in inflammatory events has been constantly increased ever since. However, conflicting results of several trials with anti-inflammatory treatments led to the conclusions that inflammation does participate in the progression of HFrEF, but more likely it is not the primary event. Conversely, it has been suggested that inflammation drives the development of HF with preserved ejection fraction (HFpEF). Recently the pharmacological blockade of interleukin-1 has been shown to prevent HF hospitalization and mortality in patients with prior myocardial infarction, lending renewed support to the hypothesis that inflammation is a promising therapeutic target in HF. Inflammation has also been proposed to underlie both HF and commonly associated conditions, such as chronic kidney disease or cancer. Within this last paradigm, an emergent role has been ascribed to clonal hematopoiesis of indeterminate potential. Here, we summarize the recent evidence about the role of inflammation in HF, highlighting the similarities and differences in HFrEF vs. HFpEF, and discuss the diagnostic and therapeutic opportunities raised by antinflammatory-based approaches.
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- 2020
28. FoxO1–Dio2 signaling axis governs cardiomyocyte thyroid hormone metabolism and hypertrophic growth
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Sergio Lavandero, Anwarul Ferdous, Annie Nguyen, Gabriele G. Schiattarella, Xiang Luo, Yuxuan Luo, Zhao V. Wang, Herman I. May, Thomas G. Gillette, Francisco Altamirano, Beverly A. Rothermel, Pavan K. Battiprolu, Joseph A. Hill, Dan L. Li, Ferdous, A., Wang, Z. V., Luo, Y., Li, D. L., Luo, X., Schiattarella, G. G., Altamirano, F., May, H. I., Battiprolu, P. K., Nguyen, A., Rothermel, B. A., Lavandero, S., Gillette, T. G., and Hill, J. A.
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0301 basic medicine ,Thyroid Hormones ,endocrine system ,Science ,General Physics and Astronomy ,DIO2 ,Cardiomegaly ,FOXO1 ,030204 cardiovascular system & hematology ,Biology ,Iodide Peroxidase ,Article ,General Biochemistry, Genetics and Molecular Biology ,Mice ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Animals ,Myocytes, Cardiac ,lcsh:Science ,Ventricular remodeling ,Cells, Cultured ,Mice, Knockout ,Multidisciplinary ,Ventricular Remodeling ,Forkhead Box Protein O1 ,FOXO Family ,General Chemistry ,medicine.disease ,Rats ,Cell biology ,Thyroid diseases ,Cardiac hypertrophy ,030104 developmental biology ,Animals, Newborn ,Gene Expression Regulation ,Cardiovascular and Metabolic Diseases ,cardiovascular system ,FOXO3 ,lcsh:Q ,Signal transduction ,hormones, hormone substitutes, and hormone antagonists ,Homeostasis ,Signal Transduction ,Hormone - Abstract
Forkhead box O (FoxO) proteins and thyroid hormone (TH) have well established roles in cardiovascular morphogenesis and remodeling. However, specific role(s) of individual FoxO family members in stress-induced growth and remodeling of cardiomyocytes remains unknown. Here, we report that FoxO1, but not FoxO3, activity is essential for reciprocal regulation of types II and III iodothyronine deiodinases (Dio2 and Dio3, respectively), key enzymes involved in intracellular TH metabolism. We further show that Dio2 is a direct transcriptional target of FoxO1, and the FoxO1–Dio2 axis governs TH-induced hypertrophic growth of neonatal cardiomyocytes in vitro and in vivo. Utilizing transverse aortic constriction as a model of hemodynamic stress in wild-type and cardiomyocyte-restricted FoxO1 knockout mice, we unveil an essential role for the FoxO1–Dio2 axis in afterload-induced pathological cardiac remodeling and activation of TRα1. These findings demonstrate a previously unrecognized FoxO1–Dio2 signaling axis in stress-induced cardiomyocyte growth and remodeling and intracellular TH homeostasis., Disease stress-induced cardiac hypertrophy is a major mechanism of pathological cardiac remodeling. Here, the authors unveil a previously unrecognized role of a FoxO1–Dio2 signaling axis in maladaptive, afterload-induced cardiac hypertrophy and intracellular thyroid hormone homeostasis.
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- 2020
29. Can hfpef and hfref coexist?
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Gabriele G. Schiattarella, Dan Tong, Joseph A. Hill, Schiattarella, G. G., Tong, D., and Hill, J. A.
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medicine.medical_specialty ,Ejection fraction ,Treatment outcome ,Protease Inhibitor ,MEDLINE ,Angiotensin-Converting Enzyme Inhibitors ,Article ,Ventricular Function, Left ,Paradigm hf ,Angiotensin Receptor Antagonists ,Risk Factors ,Physiology (medical) ,Internal medicine ,Medicine ,Humans ,Hfref ,Protease Inhibitors ,Hfpef ,Paragon-hf ,Heart Failure ,Ventricular function ,Extramural ,business.industry ,Arni ,Risk Factor ,Angiotensin Receptor Antagonist ,Hfmref ,Angiotensin-Converting Enzyme Inhibitor ,Stroke Volume ,Recovery of Function ,Paradigm-hf ,Phenotype ,Treatment Outcome ,Cardiology ,Neprilysin ,Cardiology and Cardiovascular Medicine ,business ,Human - Published
- 2020
30. Feeding Diastolic Dysfunction: Is It a Bug?
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Gabriele G. Schiattarella, Giovanni Esposito, Esposito, G., and Schiattarella, G. G.
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medicine.medical_specialty ,Heart Diseases ,Fibrosi ,Diastole ,Inflammation ,TMAO ,Choline ,Mice ,Internal medicine ,medicine ,microbiota ,Animals ,Heart Failure ,business.industry ,Animal ,Stroke Volume ,medicine.disease ,HFpEF ,Fibrosis ,Diet ,Heart Disease ,Heart failure ,mouse models of cardiovascular disease ,Cardiology ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business - Published
- 2020
31. Microbial metabolites as predictive biomarkers: a paradigm shift for cardiovascular risk stratification
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Bruno Trimarco, Gabriele G. Schiattarella, Schiattarella, G. G., and Trimarco, B.
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Oncology ,medicine.medical_specialty ,Prognosi ,business.industry ,Lysine ,Risk Factor ,Biomarker ,Stratification (mathematics) ,Methylamine ,Cardiovascular Diseases ,Paradigm shift ,Internal medicine ,Risk stratification ,medicine ,Acute Coronary Syndrome ,Cardiology and Cardiovascular Medicine ,business ,Human ,Predictive biomarker - Published
- 2019
32. Polycystin-1 Assembles With Kv Channels to Govern Cardiomyocyte Repolarization and Contractility
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Thomas G. Gillette, Joseph A. Hill, Sergii Kyrychenko, César A. Ramírez-Sarmiento, Sergio Lavandero, Kristin M. French, Soo Young Kim, Gabriele G. Schiattarella, Felipe Engelberger, Jay W. Schneider, Francisco Altamirano, Elisa Villalobos, Dan Tong, Altamirano, F., Schiattarella, G. G., French, K. M., Kim, S. Y., Engelberger, F., Kyrychenko, S., Villalobos, E., Tong, D., Schneider, J. W., Ramirez-Sarmiento, C. A., Lavandero, S., Gillette, T. G., and Hill, J. A.
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endocrine system ,TRPP Cation Channels ,Autosomal dominant polycystic kidney disease ,Action Potentials ,Mice, Transgenic ,030204 cardiovascular system & hematology ,urologic and male genital diseases ,Kv1.5 potassium channel ,Article ,Contractility ,03 medical and health sciences ,Mice ,0302 clinical medicine ,action potential ,Physiology (medical) ,medicine ,ryanodine receptor ,Repolarization ,Animals ,Humans ,L-type calcium channel ,Kv2.1 potassium channel ,Myocytes, Cardiac ,030212 general & internal medicine ,Kv4.3 potassium channel ,voltage-gated potassium channel ,Mice, Knockout ,urogenital system ,Ryanodine receptor ,business.industry ,Animal ,Voltage-gated potassium channel ,medicine.disease ,female genital diseases and pregnancy complications ,Transmembrane protein ,Cell biology ,Potassium Channels, Voltage-Gated ,embryonic structures ,cardiovascular system ,Channel (broadcasting) ,Cardiology and Cardiovascular Medicine ,business ,Human - Abstract
BACKGROUND: Polycystin-1 (PC1) is a transmembrane protein originally identified in autosomal dominant polycystic kidney disease where it regulates the calcium-permeant cation channel polycystin-2. Autosomal dominant polycystic kidney disease patients develop renal failure, hypertension, left ventricular hypertrophy, and diastolic dysfunction, among other cardiovascular disorders. These individuals harbor PC1 loss-of-function mutations in their cardiomyocytes, but the functional consequences are unknown. PC1 is ubiquitously expressed, and its experimental ablation in cardiomyocyte-specific knockout mice reduces contractile function. Here, we set out to determine the pathophysiological role of PC1 in cardiomyocytes. METHODS: Wild-type and cardiomyocyte-specific PC1 knockout mice were analyzed by echocardiography. Excitation-contraction coupling was assessed in isolated cardiomyocytes and human embryonic stem cell-derived cardiomyocytes, and functional consequences were explored in heterologous expression systems. Protein-protein interactions were analyzed biochemically and by means of ab initio calculations. RESULTS: PC1 ablation reduced action potential duration in cardiomyocytes, decreased Ca2+ transients, and myocyte contractility. PC1-deficient cardiomyocytes manifested a reduction in sarcoendoplasmic reticulum Ca2+ stores attributable to a reduced action potential duration and sarcoendoplasmic reticulum Ca2+ ATPase (SERCA) activity. An increase in outward K+ currents decreased action potential duration in cardiomyocytes lacking PC1. Overexpression of full-length PC1 in HEK293 cells significantly reduced the current density of heterologously expressed Kv4.3, Kv1.5 and Kv2.1 potassium channels. PC1 C terminus inhibited Kv4.3 currents to the same degree as full-length PC1. Additionally, PC1 coimmunoprecipitated with Kv4.3, and a modeled PC1 C-terminal structure suggested the existence of 2 docking sites for PC1 within the N terminus of Kv4.3, supporting a physical interaction. Finally, a naturally occurring human mutant PC1R4228X manifested no suppressive effects on Kv4.3 channel activity. CONCLUSIONS: Our findings uncover a role for PC1 in regulating multiple Kv channels, governing membrane repolarization and alterations in SERCA activity that reduce cardiomyocyte contractility.
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- 2019
33. Fibroblast Primary Cilia are Required for Cardiac Fibrosis
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Lorena García, Hesham A. Sadek, Ngoc Uyen Nhi Nguyen, Guillermo Díaz-Araya, Sergio Lavandero, Elisa Villalobos, Kristin M. French, Juan Carlos Roa, Herman I. May, Anwarul Ferdous, Thomas G. Gillette, Gabriele G. Schiattarella, Joseph A. Hill, Simon J. Conway, Diego Romero, Francisco Altamirano, Alfredo Criollo, Nan Jiang, Eugenia Morselli, Villalobos, E., Criollo, A., Schiattarella, G. G., Altamirano, F., French, K. M., May, H. I., Jiang, N., Nguyen, N. U. N., Romero, D., Roa, J. C., Garcia, L., Diaz-Araya, G., Morselli, E., Ferdous, A., Conway, S. J., Sadek, H. A., Gillette, T. G., Lavandero, S., and Hill, J. A.
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Male ,Cardiac fibrosis ,Fibrosi ,Myocardial Infarction ,Kinesins ,030204 cardiovascular system & hematology ,fibroblast ,Mice ,0302 clinical medicine ,Fibrosis ,TGF-beta ,Mice, Knockout ,0303 health sciences ,Primary (chemistry) ,Ventricular Remodeling ,Cilium ,Kinesin ,3T3 Cells ,Polycystic Kidney, Autosomal Dominant ,Cell biology ,medicine.anatomical_structure ,PKD1 protein ,Cardiology and Cardiovascular Medicine ,Human ,Signal Transduction ,Heart Injurie ,Cell type ,TRPP Cation Channels ,Myocardial Reperfusion Injury ,Article ,TRPP Cation Channel ,Transforming Growth Factor beta1 ,03 medical and health sciences ,Fetal Heart ,Physiology (medical) ,TGF beta signaling pathway ,medicine ,Animals ,Humans ,Cilia ,Smad3 Protein ,3T3 Cell ,Fibroblast ,030304 developmental biology ,business.industry ,Animal ,Myocardium ,Atrial Remodeling ,Fibroblasts ,medicine.disease ,Rats ,Mice, Inbred C57BL ,Animals, Newborn ,Heart Injuries ,Rat ,business - Abstract
Background: The primary cilium is a singular cellular structure that extends from the surface of many cell types and plays crucial roles in vertebrate development, including that of the heart. Whereas ciliated cells have been described in developing heart, a role for primary cilia in adult heart has not been reported. This, coupled with the fact that mutations in genes coding for multiple ciliary proteins underlie polycystic kidney disease, a disorder with numerous cardiovascular manifestations, prompted us to identify cells in adult heart harboring a primary cilium and to determine whether primary cilia play a role in disease-related remodeling. Methods: Histological analysis of cardiac tissues from C57BL/6 mouse embryos, neonatal mice, and adult mice was performed to evaluate for primary cilia. Three injury models (apical resection, ischemia/reperfusion, and myocardial infarction) were used to identify the location and cell type of ciliated cells with the use of antibodies specific for cilia (acetylated tubulin, γ-tubulin, polycystin [PC] 1, PC2, and KIF3A), fibroblasts (vimentin, α-smooth muscle actin, and fibroblast-specific protein-1), and cardiomyocytes (α-actinin and troponin I). A similar approach was used to assess for primary cilia in infarcted human myocardial tissue. We studied mice silenced exclusively in myofibroblasts for PC1 and evaluated the role of PC1 in fibrogenesis in adult rat fibroblasts and myofibroblasts. Results: We identified primary cilia in mouse, rat, and human heart, specifically and exclusively in cardiac fibroblasts. Ciliated fibroblasts are enriched in areas of myocardial injury. Transforming growth factor β-1 signaling and SMAD3 activation were impaired in fibroblasts depleted of the primary cilium. Extracellular matrix protein levels and contractile function were also impaired. In vivo, depletion of PC1 in activated fibroblasts after myocardial infarction impaired the remodeling response. Conclusions: Fibroblasts in the neonatal and adult heart harbor a primary cilium. This organelle and its requisite signaling protein, PC1, are required for critical elements of fibrogenesis, including transforming growth factor β-1–SMAD3 activation, production of extracellular matrix proteins, and cell contractility. Together, these findings point to a pivotal role of this organelle, and PC1, in disease-related pathological cardiac remodeling and suggest that some of the cardiovascular manifestations of autosomal dominant polycystic kidney disease derive directly from myocardium-autonomous abnormalities.
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- 2019
34. Novel Basic Science Insights to Improve the Management of Heart Failure: Review of the Working Group on Cellular and Molecular Biology of the Heart of the Italian Society of Cardiology
- Author
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Roberta Paolillo, Edoardo Bertero, Gabriele G. Schiattarella, Margherita Torchio, Daniele Rodolico, Sebastiano Sciarretta, Cristina Basso, Pietro Ameri, Maurizio Forte, Vittoria Di Mauro, Daniele Torella, Lia Crotti, Daniele Catalucci, Cristina Chimenti, Cinzia Perrino, Ciro Indolfi, Ameri, P, Schiattarella, G, Crotti, L, Torchio, M, Bertero, E, Rodolico, D, Forte, M, Di Mauro, V, Paolillo, R, Chimenti, C, Torella, D, Catalucci, D, Sciarretta, S, Basso, C, Indolfi, C, Perrino, C, Ameri, P., Schiattarella, G. G., Crotti, L., Torchio, M., Bertero, E., Rodolico, D., Forte, M., Di Mauro, V., Paolillo, R., Chimenti, C., Torella, D., Catalucci, D., Sciarretta, S., Basso, C., Indolfi, C., and Perrino, C.
- Subjects
0301 basic medicine ,Basic science ,Review ,030204 cardiovascular system & hematology ,Translational Research, Biomedical ,lcsh:Chemistry ,Drug Delivery Systems ,0302 clinical medicine ,Mechanisms ,Myocytes, Cardiac ,lcsh:QH301-705.5 ,Societies, Medical ,Spectroscopy ,High potential ,Microbiota ,Translational ,Disease Management ,General Medicine ,Prognosis ,3. Good health ,Computer Science Applications ,Italy ,medicine.medical_specialty ,Management of heart failure ,mechanism ,Heart failure ,Translational research ,Catalysis ,Prognostic stratification ,Inorganic Chemistry ,03 medical and health sciences ,Basic ,Research ,Autophagy ,medicine ,Animals ,Humans ,Genetic Predisposition to Disease ,ddc:610 ,Physical and Theoretical Chemistry ,Intensive care medicine ,Molecular Biology ,Inflammation ,business.industry ,Organic Chemistry ,MED/11 - MALATTIE DELL'APPARATO CARDIOVASCOLARE ,030104 developmental biology ,lcsh:Biology (General) ,lcsh:QD1-999 ,Cardiovascular and Metabolic Diseases ,business - Abstract
Despite important advances in diagnosis and treatment, heart failure (HF) remains a syndrome with substantial morbidity and dismal prognosis. Although implementation and optimization of existing technologies and drugs may lead to better management of HF, new or alternative strategies are desirable. In this regard, basic science is expected to give fundamental inputs, by expanding the knowledge of the pathways underlying HF development and progression, identifying approaches that may improve HF detection and prognostic stratification, and finding novel treatments. Here, we discuss recent basic science insights that encompass major areas of translational research in HF and have high potential clinical impact.
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- 2020
35. Epigenetic modulation of vascular diseases: Assessing the evidence and exploring the opportunities
- Author
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Péter Ferdinandy, Sophie Van Linthout, Cinzia Perrino, Thomas Thum, Gabriele G. Schiattarella, Rosalinda Madonna, Rainer Schulz, A, Schiattarella G. G., R., Madonna, Linthout, Van, Thum, S, Schulz, T., Ferdinandy, R., and Perrino, P.
- Subjects
0301 basic medicine ,Pharmacology ,Regulation of gene expression ,biology ,Physiology ,Context (language use) ,endothelial cells ,Cell biology ,cardiovascular diseases ,smooth muscle cells ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,Histone ,chemistry ,Gene expression ,biology.protein ,State of art ,Molecular Medicine ,Epigenetics ,Transcription factor ,DNA - Abstract
Vascular adaptations to either physiological or pathophysiological conditions commonly require gene expression modifications in the most represented cellular elements of the vessel wall, i.e. endothelial and smooth muscle cells. In addition to transcription factors, a number of mechanisms contribute to the regulation of gene expression in these cells including noncoding RNAs, histone and DNA modifications, collectively indicated as epigenetic modifications. Here, we summarize the state of art regarding the role of epigenetic changes in major vascular diseases, and discuss the potential diagnostic and therapeutic applications of epigenetic modulation in this context.
- Published
- 2018
36. Perivascular fibrosis and the microvasculature of the heart. Still hidden secrets of pathophysiology?
- Author
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Cinzia Perrino, Jean-Sébastien Hulot, Kirsti Ytrehus, Gabriele G. Schiattarella, Rosalinda Madonna, Ytrehus, K., Hulot, J. -S., Perrino, C., Schiattarella, G. G., and Madonna, R.
- Subjects
0301 basic medicine ,Pharmacology ,Pathology ,medicine.medical_specialty ,Physiology ,Cardiac fibrosis ,business.industry ,Connective tissue ,Disease ,030204 cardiovascular system & hematology ,medicine.disease ,Pathophysiology ,Cardiac dysfunction ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,cardiovascular system ,medicine ,Molecular Medicine ,business ,Perivascular fibrosis - Abstract
Perivascular fibrosis, the deposition of connective tissue around the vessels, has been demonstrated crucially involved in the development of cardiac dysfunction. Although cardiac fibrosis has been shown to be reversible under certain experimental conditions, effective anti-fibrotic therapies remain largely elusive. Therefore, perivascular fibrosis currently represents a major therapeutic target for cardiovascular diseases. The main topic of this review will be to address the mechanisms underlying perivascular fibrosis of the vasculature within the myocardium, with a special focus on perivascular fibrosis of small vessels, microvascular dysfunction and disease.
- Published
- 2018
37. Inflammation in aortic stenosis: Shaping the biomarkers network
- Author
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Gabriele G. Schiattarella, Cinzia Perrino, Schiattarella, G. G., and Perrino, C.
- Subjects
medicine.medical_specialty ,MEDLINE ,Inflammation ,TAVR ,Article ,Muscle hypertrophy ,Transcatheter Aortic Valve Replacement ,Internal medicine ,medicine ,Humans ,Cytokine ,Cardiac remodeling ,business.industry ,Biomarker ,Hypertrophy ,Aortic Valve Stenosis ,medicine.disease ,Aortic Valve Stenosi ,Stenosis ,Aortic Valve ,Aortic valve surgery ,Cardiology ,Cytokines ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,Biomarkers ,Human - Abstract
OBJECTIVE: Previous studies have suggested that cytokines and growth factors may predict ventricular recovery following aortic valve replacement (AVR). The primary objective of this study was to identify cytokines that predict ventricular recovery following transcatheter AVR (TAVR). METHODS: We prospectively enrolled 121 consecutive patients who underwent TAVR. Standard echocardiographic assessment at baseline, 1-month and 1-year after TAVR included left ventricular (LV) mass index (LVMI) and global longitudinal strain (GLS). Blood samples were obtained at the time of the procedure to measure cytokines using a 63-plex Luminex platform. Partial least squares-discriminant analysis was performed to identify cytokines associated with ventricular remodeling and function at baseline as well as 1 year after TAVR. RESULTS: The mean age was 84±9 years, with a majority of male subjects (59%), a mean LVMI of 120.4±45.1 g/m(2) and LVGLS of −13.0±3.2%. On average, LV mass decreased by 8.1% and GLS improved by 20.3% at 1 year following TAVR. Among cytokines assayed, elevated hepatocyte growth factor (HGF) emerged as a common factor significantly associated with worse baseline LVMI and GLS as well as reduced ventricular recovery (p
- Published
- 2019
38. Comparison of Baseline Characteristics and Outcomes in Men Versus Women With Aortic Stenosis Undergoing Transcatheter Aortic Valve Implantation
- Author
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Gabriele G. Schiattarella, Molly Szerlip, Paul A. Grayburn, Katherine Harrington, Anna Sannino, Sannino, A., Szerlip, M., Harrington, K., Schiattarella, G. G., and Grayburn, P. A.
- Subjects
Male ,Pacemaker, Artificial ,Sex Factor ,Coronary Artery Disease ,030204 cardiovascular system & hematology ,Severity of Illness Index ,Cohort Studies ,0302 clinical medicine ,Postoperative Complications ,Aortic valve replacement ,Retrospective Studie ,Myocardial Revascularization ,Medicine ,030212 general & internal medicine ,Aged, 80 and over ,Incidence ,Hazard ratio ,Treatment Outcome ,Cardiothoracic surgery ,Heart Valve Prosthesis ,Cohort ,Hypertension ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,Human ,Cohort study ,medicine.medical_specialty ,Aortic Valve Insufficiency ,Postoperative Hemorrhage ,Transcatheter Aortic Valve Replacement ,03 medical and health sciences ,Age Distribution ,Sex Factors ,Internal medicine ,Severity of illness ,Humans ,Mortality ,Aged ,Proportional Hazards Models ,Retrospective Studies ,business.industry ,Retrospective cohort study ,Stroke Volume ,Aortic Valve Stenosis ,medicine.disease ,Aortic Valve Stenosi ,Stenosis ,Heart Valve Prosthesi ,Proportional Hazards Model ,Postoperative Complication ,Cohort Studie ,business - Abstract
Female gender has been linked to increased risk of adverse events after surgical aortic valve replacement; however, the evidence regarding the role of gender differences on clinical outcomes in patients who underwent transcatheter aortic valve implantation (TAVI) is still debated. This retrospective study included 910 consecutive patients with severe, symptomatic aortic stenosis who underwent TAVI in 2 institutions from January 2012 to July 2016. The primary end point was all-cause mortality at 1 year after TAVI in women versus men. Women had a higher incidence of in-hospital vascular complications (7.8% vs 4.1%) and major or life-threatening bleeding (4.0% vs 1.6%) than men. At 1 year, women showed a lower mortality rate than men (7.0% vs 12.7%, adjusted hazard ratio [HR] 0.42, 95% confidence interval [CI] [0.23 to 0.76], p = 0.004). When stratifying by specific subgroups of interest, the survival benefit in women persisted in (1) patients with a Society of Thoracic Surgery risk score ≤ 8 (adjusted HR 0.35, 95% CI [0.14 to 0.88], p = 0.026); (2) patients treated with first-generation devices (adjusted HR 0.46, 95% CI [0.24 to 0.86], p = 0.016); and (3) patients treated with balloon-expandable valves (adjusted HR 0.40, 95% CI [0.19 to 0.86], p = 0.019). In conclusion, in this large patient cohort, women had lower 1-year mortality after TAVI than men, particularly with an STS score ≤ 8, or treated with first-generation and balloon-expandable devices.
- Published
- 2017
39. Rotational atherectomy for the treatment of isolated femoral artery traumatic lesion: a case report
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Anna Sannino, Cinzia Perrino, Giovanni Esposito, Giuseppe Gargiulo, Massimo Chiariello, Luigi Di Serafino, Gabriele G. Schiattarella, Anna Franzone, Esposito, Giovanni, Di Serafino, L., Gargiulo, G., Sannino, A., Schiattarella, G. G., Franzone, A., Perrino, Cinzia, and Chiariello, M.
- Subjects
Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,lcsh:Medicine ,Femoral artery ,Rotational atherectomy ,Lesion ,medicine.artery ,Medicine ,rotational atherectomy ,claudicatio intermittens ,medicine.diagnostic_test ,business.industry ,lcsh:R ,food and beverages ,medicine.disease ,Intermittent claudication ,Surgery ,Peripheral ,Stenosis ,trauma ,Angiography ,Radiology ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,Complication - Abstract
We describe the case of a 50-year-old man with an isolated plaque of the left distal superficial femoral artery (SFA), probably not related to atherosclerosis, but rather to a traumatic event. He was admitted to our hospital because of intermittent claudication. The critical distal SFA stenosis was documented by angiography and the lesion was treated by rotational atherectomy without stent implantation. At 1-year follow up, Doppler Ultrasound scan demonstrated a normal flow pattern of the left SFA and downstream districts in the absence of any complication. Therefore, rotational atherectomy is a safe and effective technique particularly in cases of peripheral arterial disease wherein stent implantation is dangerous.
- Published
- 2016
40. Therapeutic Targeting of Autophagy in Cardiovascular Disease
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Joseph A. Hill, Gabriele G. Schiattarella, Schiattarella, G. G., and Hill, J. A.
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0301 basic medicine ,medicine.medical_specialty ,Cell type ,Cell ,Cellular homeostasis ,Heart failure ,Antineoplastic Agents ,Apoptosis ,Disease ,030204 cardiovascular system & hematology ,Biology ,Article ,Antineoplastic Agent ,Translational Research, Biomedical ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Cardiovascular Disease ,Internal medicine ,medicine ,Autophagy ,Animals ,Humans ,Myocytes, Cardiac ,Molecular Targeted Therapy ,Molecular Biology ,Animal ,Risk Factor ,Apoptosi ,Lysosome ,Remodeling ,Cardiac hypertrophy ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,Cytoplasm ,Cardiovascular Diseases ,Signal transduction ,Cardiology and Cardiovascular Medicine ,Lysosomes ,Neuroscience ,Intracellular ,Human ,Signal Transduction - Abstract
Autophagy is an evolutionarily ancient process of intracellular catabolism necessary to preserve cellular homeostasis in response to a wide variety of stresses. In the case of post-mitotic cells, where cell replacement is not an option, finely tuned quality control of cytoplasmic constituents and organelles is especially critical. And due to the ubiquitous and critical role of autophagic flux in the maintenance of cell health, it comes as little surprise that perturbation of the autophagic process is observed in multiple disease processes. A large body of preclinical evidence suggests that autophagy is a double-edged sword in cardiovascular disease, acting in either beneficial or maladaptive ways, depending on the context. In light of this, the autophagic machinery in cardiomyocytes and other cardiovascular cell types has been proposed as a potential therapeutic target. Here, we summarize current knowledge regarding the dual functions of autophagy in cardiovascular disease. We go on to analyze recent evidence suggesting that titration of autophagic flux holds potential as a novel treatment strategy.
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- 2015
41. Use of statins in lower extremity artery disease: a review
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Gabriele G. Schiattarella, Anna Sannino, Bruno Trimarco, Giovanni Esposito, Fernando Scudiero, Marco Ferrone, Bruno Amato, Andreina Carbone, Lorenzo Chiariotti, Roberto Vincenzo Corrado, Federica Serino, Giuseppe Giugliano, Giuseppe Gargiulo, Raffaele Izzo, Linda Brevetti, Cinzia Perrino, Gargiulo, G., Giugliano, Giuseppe, Brevetti, L., Sannino, A., Schiattarella, G. G., Serino, F., Carbone, A., Scudiero, F., Ferrone, M., Corrado, R., Izzo, Raffaele, Chiariotti, Lorenzo, Perrino, Cinzia, Amato, Bruno, Trimarco, Bruno, and Esposito, Giovanni
- Subjects
medicine.medical_specialty ,Treatment outcome ,lcsh:Surgery ,Disease ,Pentoxifylline ,Peripheral Arterial Disease ,Quality of life ,Humans ,Medicine ,business.industry ,lcsh:RD1-811 ,General Medicine ,Lower extremity artery ,Cilostazol ,Surgery ,Treatment Outcome ,Lower Extremity ,Cardiovascular and Metabolic Diseases ,Quality of Life ,lipids (amino acids, peptides, and proteins) ,Statin therapy ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,business ,Pravastatin ,Research Article ,medicine.drug - Abstract
Background Lower extremity artery disease (LE-PAD) is one of the most common manifestations of atherosclerosis, particularly in elderly patients, and it is related to a high cardiovascular risk. Description It is well established that statin therapy is characterized by crucial benefits on cardiovascular system by limiting atherosclerotic progression and reducing cardiovascular events and mortality. A growing body of evidence support efficacy of statins in LE-PAD due to the ability of both reducing cardiovascular risk and improving walking distance and, hence, quality of life. Consequently, statin therapy should be considered in all LE-PAD patients and new LDL-cholesterol targets should be reached. Conclusions Our opinion is that statin therapy remains still underutilized or with inadequate dosage, so therapy of LE-PAD patients should be improved to obtain all the demonstrated benefits of statins.
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- 2012
42. Molecular modulation of post-ischemic cardiac remodeling by hindlimb ischemia
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Esposito, G., Gabriele Schiattarella, Perrino, C., Franzone, A., Sannino, A., Gargiulo, G., Pironti, G., Cannavo, A., Zambrano, N., Chiariello, M., Esposito, Giovanni, Schiattarella, G. G., Perrino, Cinzia, Franzone, A., Sannino, A., Gargiulo, G., Pironti, G., Cannavo, A., Zambrano, N., and C. h. i. a. r. i. e. l. l. o., M.
- Published
- 2010
43. Il secondo messaggero cAMP e la regolazione della funzione cardiaca: ruolo dell'adenilato ciclasi
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Capretti G., Franzone A., Schiattarella G.G., Gargiulo G., Sannino A., Sorrentino S., Chiariello M., PERRINO, CINZIA, ESPOSITO, GIOVANNI, Capretti, G., Franzone, A., Schiattarella, G. G., Gargiulo, G., Sannino, A., Sorrentino, S., Perrino, Cinzia, Esposito, Giovanni, and Chiariello, M.
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cAMP - Published
- 2009
44. Prevenzione della restenosi e della trombosi intrastent: ruolo del derivato acridinico quinacrina
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G. Gargiulo, G. Pironti, G. G. Schiattarella, L. Di Serafino, R. Guerriero, A. Sannino, G. Petrillo, PERRINO, CINZIA, CIRILLO, PLINIO, ESPOSITO, GIOVANNI, CHIARIELLO, MASSIMO, Gargiulo, G., Perrino, Cinzia, Pironti, G., Schiattarella, G. G., Di Serafino, L., Guerriero, R., Sannino, A., Petrillo, G., Cirillo, Plinio, Esposito, Giovanni, and Chiariello, Massimo
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- 2009
45. Identification of the ligands of protein interaction domains through a functional approach
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Andrea Scaloni, Danilo Allegra, Ginevra Caratù, Maria Napolitano, Tommaso Russo, Chiara D'Ambrosio, Marida Bimonte, Nicola Zambrano, Gabriele G. Schiattarella, Caratu, G, Allegra, D, Bimonte, M, SCHIATTARELLA G., G, D'Ambrosio, C, Scaloni, A, Napolitano, M, Russo, Tommaso, and Zambrano, Nicola
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Phosphotyrosine binding ,Context (language use) ,Computational biology ,Biology ,Ligands ,Biochemistry ,Analytical Chemistry ,Cell Line ,Mice ,Protein structure ,MULTIPLE SEQUENCE ALIGNMENT ,SIGNAL-TRANSDUCTION ,ORGANIZATION ,COMPLEXES ,DIVISION ,ELEGANS ,NETWORK ,PEPTIDE ,SYSTEM ,KINASE ,Protein Interaction Mapping ,Animals ,Humans ,Protein function prediction ,Phosphotyrosine ,Molecular Biology ,Adaptor Proteins, Signal Transducing ,Genetics ,Tumor Suppressor Proteins ,Cell Cycle ,Signal transducing adaptor protein ,Fibroblasts ,Ligand (biochemistry) ,Protein tertiary structure ,Protein Structure, Tertiary ,Cytoskeletal Proteins ,Receptors, LDL ,Cardiovascular and Metabolic Diseases ,Multiprotein Complexes ,NIH 3T3 Cells ,Phosphotyrosine-binding domain ,Low Density Lipoprotein Receptor-Related Protein-1 ,RGS Proteins - Abstract
The identification of protein-protein interaction networks has often given important information about the functions of specific proteins and on the cross-talk among metabolic and regulatory pathways. The availability of entire genome sequences has rendered feasible the systematic screening of collections of proteins, often of unknown function, aimed to find the cognate ligands. Once identified by genetic and/or biochemical approaches, the interaction between two proteins should be validated in the physiologic environment. Herein we describe an experimental strategy to screen collections of protein-protein interaction domains to find and validate candidate interactors. The approach is based on the assumption that the overexpression in cultured cells of protein-protein interaction domains, isolated from the context of the whole protein, could titrate the endogenous ligand and, in turn, exert a dominant negative effect. The identification of the ligand could provide us with a tool to check the relevance of the interaction because the contemporary overexpression of the isolated domain and of its ligand could rescue the dominant negative phenotype. We explored this approach by analyzing the possible dominant negative effects on the cell cycle progression of a collection of phosphotyrosine binding (PTB) domains of human proteins. Of 47 PTB domains, we found that the overexpression of 10 of them significantly interfered with the cell cycle progression of NIH3T3 cells. Four of them were used as baits to identify the cognate interactors. Among these proteins, CARM1, interacting with the PTB domain of RabGAP1, and EF1alpha, interacting with RGS12, were able to rescue the block of the cell cycle induced by the isolated PTB domain of the partner protein, thus confirming in vivo the relevance of the interaction. These results suggest that the described approach can be used for the systematic screening of the ligands of various protein-protein interaction domains also by using different biological assays.
- Published
- 2006
46. Endovascular treatment of lower extremity arteries is associated with an improved outcome in diabetic patients affected by intermittent claudication
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Vittorio Schiano, Gabriele G. Schiattarella, Giovanni Esposito, Fernando Scudiero, Federica Serino, Bruno Trimarco, Cinzia Perrino, Bruno Amato, Linda Brevetti, Anna Sannino, Andreina Carbone, Antonio Bruno, Marco Ferrone, Giuseppe Giugliano, Giuseppe Gargiulo, Giugliano, Giuseppe, Perrino, Cinzia, Schiano, V., Brevetti, L., Sannino, A., Schiattarella, G. G., Gargiulo, G., Serino, F., Ferrone, M., Scudiero, F., Carbone, A., Bruno, A., Amato, Bruno, Trimarco, Bruno, Esposito, Giovanni, Giugliano G., Perrino C., Schiano V., Brevetti L., Sannino A., Schiattarella G.G., Gargiulo G., Serino F., Ferrone M., Scudiero F., Carbone A., Bruno A., Amato B., Trimarco B., and Esposito G.
- Subjects
Carotid Artery Diseases ,Male ,medicine.medical_treatment ,Myocardial Infarction ,Coronary Artery Disease ,Kaplan-Meier Estimate ,Walking ,Coronary artery disease ,Prospective Studies ,Stroke ,education.field_of_study ,General Medicine ,Middle Aged ,Treatment Outcome ,Lower Extremity ,Cardiology ,Female ,medicine.symptom ,Human ,Research Article ,medicine.medical_specialty ,Diabetic Angiopathie ,Population ,lcsh:Surgery ,Diabetic angiopathy ,Revascularization ,Follow-Up Studie ,Peripheral Arterial Disease ,Internal medicine ,Angioplasty ,medicine ,Humans ,education ,Aged ,Proportional Hazards Models ,Carotid Artery Disease ,business.industry ,lcsh:RD1-811 ,Critical limb ischemia ,Intermittent Claudication ,medicine.disease ,Intermittent claudication ,Surgery ,Prospective Studie ,Death, Sudden, Cardiac ,Cardiovascular and Metabolic Diseases ,Proportional Hazards Model ,business ,Diabetic Angiopathies ,Follow-Up Studies - Abstract
Background Lower extremity peripheral arterial disease (LE-PAD) is a highly prevalent condition among diabetic patients, associated with reduced walking capacity and a high incidence of cardiovascular events. Endovascular revascularization of lower extremities arteries improves walking performance and quality of life of diabetic patients affected by intermittent claudication, but few studies evaluated the impact of revascularization on cardiovascular outcome in this high-risk population. Accordingly, in the present study we evaluated if leg-ischemia resolution by effective lower limbs percutaneous revascularization can also impact cardiovascular outcome in a homogeneous group of diabetic patients affected by intermittent claudication. Methods 236 diabetic patients affected by LE-PAD at stage II of Fontaine’s classification, with ankle/brachial index ≤0.90 and one or more hemodynamically significant stenosis in at least one artery of the ileo-femoro-popliteal axis were enrolled in the study. According to the Trans-Atlantic Inter Society Consensus II recommendations, 123 (52.1%) underwent percutaneous transluminal angioplasty (PTA group), while 113 (47.9%) underwent conservative medical therapy only (MT group). The incidence of major cardiovascular events (cardiovascular death, myocardial infarction, ischemic stroke, coronary or carotid revascularization) was prospectively analyzed with Kaplan-Meier curves and the risk of developing a cardiovascular event calculated by Cox analyses. Results No baseline difference in cardiovascular risk factors were observed between the PTA and MT groups, except for a lower prevalence of males in PTA group (74.8% vs. 85.8%, p=0.034). Furthermore, patients in the PTA group showed a worse walking capacity as expressed by maximum walking distance (108.7 ± 300.9 vs 378.4 ± 552.3 meters, p Conclusions The present study shows that lower limbs revascularization of diabetic patients affected by intermittent claudication, in addition to improve walking performance, is associated with a reduction in the incidence of future major cardiovascular events.
- Published
- 2012
47. Moderate to severe mitral regurgitation in patients undergoing trancatheter aortic valve replacement: a meta-analysis of mortality outcomes and mitral regurgitation evolution in 4,933 patients
- Author
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Sannino, A., Losi, M. -A, Gabriele Schiattarella, Gargiulo, G., Perrino, C., Stabile, E., Cirillo, P., Imbriaco, M., Trimarco, B., Esposito, G., Sannino, A (Sannino, A.)[ 1 ], Losi, MA (Losi, M. -A.)[ 1 ], Schiattarella, GG (Schiattarella, G. G.)[ 1 ], Gargiulo, G (Gargiulo, G.)[ 1 ], Perrino, C (Perrino, C.)[ 1 ], Stabile, E (Stabile, E.)[ 1 ], Cirillo, P (Cirillo, P.)[ 1 ], Imbriaco, M (Imbriaco, M.)[ 1 ], Trimarco, B (Trimarco, B.)[ 1 ], Esposito, G (Esposito, G.), Sannino, Anna, Losi, MARIA ANGELA, Schiattarella, GABRIELE GIACOMO, Gargiulo, Giuseppe, Perrino, Cinzia, Stabile, Eugenio, Cirillo, Plinio, Imbriaco, Massimo, Trimarco, Bruno, and Esposito, Giovanni
48. Induction of mitogen activated protein kinases in response to pressure overload: a novel possible biomarker for uncontrolled human hypertension
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Franzone, A., Esposito, G., Capretti, G., Gabriele Schiattarella, Cannavo, A., Pironti, G., Di Serafino, L., Perrino, C., Chiariello, M., Franzone, A., Esposito, Giovanni, Capretti, G., Schiattarella, G. G., Cannavo, A., Pironti, G., Di Serafino, L., Perrino, Cinzia, and Chiariello, Massimo
49. AKAP121 controls mitochondrial function and survival of cardiomyocytes
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Gabriele Schiattarella, Perrino, C., Gargiulo, G., Pironti, G., Feliciello, A., Saviano, M., Zaccaro, L., Guerriero, R., Esposito, G., Chiariello, M., Schiattarella, G. G., Perrino, Cinzia, Gargiulo, G., Pironti, G., Feliciello, Antonio, Saviano, M., Zaccaro, L., Guerriero, R., Esposito, Giovanni, and Chiariello, Massimo
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