MARIA ALFARANO

Dottoressa di ricerca

ciclo: XXXV

supervisore: Prof. Andrea Frustaci

Titolo della tesi: MYOCARDIAL ALDOSTERONE RECEPTORS AND AQUAPORIN 1 UP-REGULATION CAUSING CARDIOMYOCYTE REMODELING IN HUMAN HEART FAILURE

Background: Abnormal aldosterone signaling is a recognized source of cardio-vascular damage. Its influence on cardiomyocyte structure, function and hormonal receptors when associated with heart failure is still unreported. Methods: Twenty-six consecutive patients with heart failure (LVEF < 40%), normal coronaries and valves, underwent a left ventricular endomyocardial biopsy (EMB) for evaluation of myocardial substrate. Biopsy samples were processed for histology, electron microscopy, immunohistochemistry, and Western Blot analysis of myocardial aldosterone receptors and aquaporin-1 correlated with plasma aldosterone (AD) and renin activity (PRA). Eight patients with virus-negative inflammatory cardiomyopathy (ICM), had a control EMB after 6 months of immunosuppressive therapy and recovery of cardiac function with re-evaluation of cardiomyocyte structure and receptor expression. Results: EMB in addition to the diagnosis of myocarditis (15 cases), dilated cardiomyopathy (CM, 6), alcohol CM (2), diabetic CM (3), showed vacuolar degeneration and cloudy swelling of cardiomyocytes corresponding at electron microscopy to ions and water accumulation into cytosol, membrane-bound vesicles, nucleus and other organelles, associated to an increased AD, PRA and myocardial expression of aldosterone receptors (2.3 fold) and aquaporin 1 (2.6 fold). In the 8 pts recovered from ICM, cardiomyocyte diameter reduced with disappearance of intracellular vacuoles, normalization of cytosol, nucleus and cell organelles’ electron-density, along with down-regulation of aldosterone receptors and aquaporin-1. Conclusion: Human heart failure is associated with over-expression of myocyte aldosterone receptors and aquaporin-1 causing intracellular water overloading, swelling and functional compromise of cardiomyocytes. Cardiac recovery is accompanied by down-regulation of hormonal receptors and normalization of cell structure and composition. Key words: hyperaldosteronism, myocardial damage, heart failure, aldosterone receptors, aquaporin-1, vacuolar degeneration, cloudy swelling, cell volume control, cellular and molecular rehabilitation.

Produzione scientifica

11573/1727524 - 2024 - Endomyocardial biopsy: safety and prognostic utility in paediatric and adult myocarditis in the European Society of Cardiology EURObservational Research Programme Cardiomyopathy and Myocarditis Long-Term Registry

Caforio, Alida L P; Kaski, Juan P; Gimeno, Juan R; Elliott, Perry M; Laroche, Cecile; Tavazzi, Luigi; Tendera, Michal; Fu, Michael; Sala, Simone; Seferovic, Petar M; Heliö, Tiina; Calò, Leonardo; Blagova, Olga; Amin, Ahmad; Kindermann, Ingrid; Sinagra, Gianfranco; Frustaci, Andrea; Bonnet, Daniel; Charron, Philippe; Maggioni, Aldo P; Null, Null; Ferrari, R; Alonso, A; Bax, J; Blomström-Lundqvist, C; Gielen, S; Lancellotti, P; Maggioni, A P; Maniadakis, N; Pinto, F; Ruschitzka, F; Tavazzi, L; Vardas, P; Weidinger, F; Zeymer, U; Vahanian, A; Budaj, A; Dagres, N; Danchin, N; Delgado, V; Emberson, J; Friberg, O; Gale, C P; Heyndrickx, G; Iung, B; James, S; Kappetein, A P; Maggioni, A P; Maniadakis, N; Nagy, K V; Parati, G; Petronio, A-S; Pietila, M; Prescott, E; Ruschitzka, F; Van De Werf, F; Weidinger, F; Zeymer, U; Gale, C P; Beleslin, B; Budaj, A; Chioncel, O; Dagres, N; Danchin, N; Emberson, J; Erlinge, D; Glikson, M; Gray, A; Kayikcioglu, M; Maggioni, A P; Nagy, K V; Nedoshivin, A; Petronio, A-P; Roos-Hesselink, J W; Wallentin, L; Zeymer, U; Popescu, B A; Adlam, D; Caforio, A L P; Capodanno, D; Dweck, M; Erlinge, D; Glikson, M; Hausleiter, J; Iung, B; Kayikcioglu, M; Ludman, P; Lund, L; Maggioni, A P; Matskeplishvili, S; Meder, B; Nagy, K V; Nedoshivin, A; Neglia, D; Pasquet, A A; Roos-Hesselink, J W; Rossello, F J; Shaheen, S M; Torbica, A; Caforio, Alida; Gimeno Blanes, Juan Ramon; Charron, Philippe; Elliott, Perry; Kaski, Juan Pablo; Maggioni, Aldo P; Tavazzi, Luigi; Tendera, Michal; Pihkala, J; Ojala, T; Hiippala, A; Jarvinen, T; Lommi, J; Helio, T; Sinisalo, J; Bonnet, D; Khraiche, D; Szezepanski, I; Charron, P; Mankikian, S; Maupain, C; Collet, J-P; Gandjbakhch, E; Kerneis, M; Pruny, J-F; Bauer, A; Pfeiffer, B; Felix, S B; Beug, D; Dorr, M; Kaczmarek, S; Lehnert, K; Pedersen, A-L; Bruder, M; Gorenflo, M; Arnold, R; Uhl, S; Ziesenitz, V; Jung, A; Roesch, E; Böhm, M; Kindermann, I; Linicus, Y; Werner, C; Neurath, B; Schild-Ungerbuehler, M; Kindermann, M; Kaski, J P; Norrish, G; Field, E; Elliott, P; Lorenzini, M; Watkinson, O; Wicks, E; Anastasakis, A; Ritsatos, K; Vlagkouli, V; Rammos, S; Kourelis, G; Giannakopoulou, A; Karanasios, E; Papachristou, P; Papadopoulos, G; Servos, G; Maleki, M; Noohi Bezanjani, F; Amin, A; Naderi, N; Parsaee, M; Taghavi, S; Ghadrdoost, B; Jafari, S; Khoshavi, M; Della Bella, P; Sala, S; Peretto, G; Calabro, R; Pacileo, G; Russo, M G; Limongelli, G; Esposito, A; Gragnano, F; Gravino, R; Marrazzo, T; Masarone, D; Pazzanese, V; Rubino, M; Tramonte, S; Valente, F; Caiazza, M; Calabro, P; Cirillo, A; Trimarco, B; Losi, M-A; Di Nardo, C; Giamundo, A; Pacelli, F; Canciello, G; Iliceto, S; Caforio, A; Calore, C; Leoni, L; Perazzolo Marra, M; Rigato, I; Tarantini, G; Schiavo, A; Testolina, M; Fedele, F; Frustaci, A; Alfarano, M; Chimenti, C; Drago, F; Baban, A; Calò, L; Lanzillo, C; Martino, A; Uguccioni, M; Zachara, E; Halasz, G; Re, F; Sinagra, G; Carriere, C; Merlo, M; Ramani, F; Kavoliuniene, A; Krivickiene, A; Tamuleviciute-Prasciene, E; Viezelis, M; Celutkiene, J; Balkeviciene, L; Laukyte, M; Paleviciute, E; Asselbergs, F; De Jonge, N; Kirkels, J H; Van Der Heijden, J; Van Laake, L; Sammani, A; Mizia-Stec, K; Tendera, M; Wybraniec, M; Czekaj, A; Sikora-Puz, A; Skoczynska, A; Rubis, P; Wisniowska-Smialek, S; Grzybowski, J; Ojrzynska, N; Bilinska, Z; Chmielewski, P; Foss-Nieradko, B; Michalak, E; Stepien-Wojno, M; Mazek, B; Brzezinska-Rajszys, G; Ziolkowska, L; Boruc, A; Plodzien, E; Rocha Lopes, L; Almeida, A R; Cruz, I; Gomes, A C; Pereira, A R; Ginghina, C; Jurcut, R; Apetrei, E; Militaru, S; Mircea Coman, I; Mursa, A; Popescu, B A; Frigy, A; Fehervari, L; Fogarasi, Z; Kocsis, I; Szabo, I A; Nikitin, I; Resnik, E; Komissarova, M; Lazarev, V; Shebzukhova, M; Ustyuzhanin, D; Blagova, O; Alieva, I; Kulikova, V; Lutokhina, Y; Pavlenko, E; Varionchik, N; Zaklyazminskaya, E; Dzemeshkevich, S; Kolbasova, E; Kotlukova, N; Rusinova, V; Ristic, A D; Sefer - 01a Articolo in rivista

rivista: EUROPEAN HEART JOURNAL (-London : Harcourt -Oxford : Oxford University Press) pp. 2548-2569 - issn: 1522-9645 - wos: WOS:001199122100001 (0) - scopus: 2-s2.0-85199330004 (3)

11573/1717291 - 2024 - Oxidative Stress in Transthyretin-Mediated Amyloidosis: An Exploratory Study

Fiore, Marco; Cambieri, Chiara; Grazia Di Certo, Maria; Libonati, Laura; Passananti, Claudio; Moret, Federica; D’Andrea, Edoardo; Gabanella, Francesca; Corbi, Nicoletta; Chimenti, Cristina; Alfarano, Maria; Ferraguti, Giampiero; Francati, Silvia; Garibaldi, Matteo; Inghilleri, Maurizio; Ceccanti, Marco - 01a Articolo in rivista

rivista: ANTIOXIDANTS (Basel: MDPI) pp. - - issn: 2076-3921 - wos: (0) - scopus: (0)

11573/1727521 - 2024 - Novel ATP2A2 gene mutation C.118g>A causing keratinocyte and cardiomyocyte disconnection in darier disease

Frustaci, Andrea; De Luca, Alessandro; Verardo, Romina; Guida, Valentina; Alfarano, Maria; Calvieri, Camilla; Sansone, Luigi; Russo, Matteo Antonio; Chimenti, Cristina - 01a Articolo in rivista

rivista: BIOMEDICINES (Basel: MDPI) pp. - - issn: 2227-9059 - wos: WOS:001232384000001 (0) - scopus: 2-s2.0-85194109960 (0)

11573/1727522 - 2024 - Immunomodulating and immunosuppressive therapy for virus-negative immune-mediated myocarditis

Frustaci, Andrea; Letizia, Claudio; Alfarano, Maria; Marchionni, Giulia; Verardo, Romina; Chimenti, Cristina - 01g Articolo di rassegna (Review)

rivista: BIOMEDICINES (Basel: MDPI) pp. - - issn: 2227-9059 - wos: WOS:001276464300001 (0) - scopus: 2-s2.0-85199593292 (0)

11573/1707594 - 2024 - Long-Term Clinical-Pathologic Results of Enzyme Replacement Therapy in Prehypertrophic Fabry Disease Cardiomyopathy

Frustaci, Andrea; Verardo, Romina; Galea, Nicola; Alfarano, Maria; Magnocavallo, Michele; Marchitelli, Livia; Sansone, Luigi; Belli, Manuel; Cristina, Mario; Frustaci, Emanuela; Russo, Matteo Antonio; Chimenti, Cristina - 01a Articolo in rivista

rivista: JOURNAL OF THE AMERICAN HEART ASSOCIATION. CARDIOVASCULAR AND CEREBROVASCULAR DISEASE (Oxford: Wiley-Blackwell) pp. - - issn: 2047-9980 - wos: WOS:001203051600023 (5) - scopus: (0)

11573/1725485 - 2024 - Thromboembolic Risk in Sinus Rhythm: A New Paradigm in Light Chain Cardiac Amyloidosis

Marchionni, G.; Costantino, J.; Ballatore, F.; Alfarano, M.; Galea, N.; Leopizzi, M.; Netti, L.; Maestrini, V.; Vizza, C. D.; Chimenti, C. - 01i Case report

rivista: JACC. CASE REPORTS (New York: Elsevier Inc.) pp. - - issn: 2666-0849 - wos: (0) - scopus: 2-s2.0-85203241699 (0)

11573/1681942 - 2023 - The Role of MicroRNA in the myocarditis. a small actor for a great role

Chimenti, Cristina; Magnocavallo, Michele; Vetta, Giampaolo; Alfarano, Maria; Manguso, Giulia; Ajmone, Francesco; Ballatore, Federico; Costantino, Jacopo; Ciaramella, Piera; Severino, Paolo; Miraldi, Fabio; Lavalle, Carlo; Vizza, Carmine Dario - 01g Articolo di rassegna (Review)

rivista: CURRENT CARDIOLOGY REPORTS (Philadelphia, PA : Current Science, c1999-) pp. 641-648 - issn: 1523-3782 - wos: WOS:000999972300001 (1) - scopus: 2-s2.0-85160862419 (2)

11573/1710389 - 2023 - [Anticoagulant therapy in left ventricular non-compaction: when, how and why]

Costantino, Jacopo; Maria Ajmone, Francesco; Maggio, Enrico; Ballatore, Federico; Manguso, Giulia; Ciaramella, Piera; Galea, Nicola; Alfarano, Maria; Severino, Paolo; Lavalle, Carlo; Vizza, Carmine Dario; Chimenti, Cristina - 01a Articolo in rivista

rivista: GIORNALE ITALIANO DI CARDIOLOGIA (ROMA: Il Pensiero Scientifico Roma : C.E.P.I. Centro editoriale pubblicitario italiano) pp. - - issn: 1972-6481 - wos: WOS:001102239600006 (1) - scopus: 2-s2.0-85175403983 (2)

11573/1706290 - 2023 - Interleukin-17A-Correlated Myocarditis in Patients with Psoriasis: Cardiac Recovery following Secukinumab Administration

Frustaci, Andrea; Galea, Nicola; Dominici, Lorenzo; Verardo, Romina; Alfarano, Maria; Scialla, Rossella; Richetta, Antonio Giovanni - 01a Articolo in rivista

rivista: JOURNAL OF CLINICAL MEDICINE (MDPI Publishing, Basel, Switzerland) pp. - - issn: 2077-0383 - wos: WOS:001017239200001 (7) - scopus: 2-s2.0-85163991813 (6)

11573/1672321 - 2023 - Infiltration of conduction tissue is a major cause of electrical instability in cardiac amyloidosis

Frustaci, Andrea; Verardo, Romina Annita; Russo, Matteo Antonio; Caldarulo, Marina; Alfarano, Maria; Galea, Nicola; Miraldi, Fabio; Chimenti, Cristina - 01a Articolo in rivista

rivista: JOURNAL OF CLINICAL MEDICINE (MDPI Publishing, Basel, Switzerland) pp. 1- - issn: 2077-0383 - wos: WOS:000947515000001 (4) - scopus: 2-s2.0-85149930309 (5)

11573/1634466 - 2022 - Prevalence and clinical Implications of COVID-19 myocarditis

Chimenti, C.; Magnocavallo, M.; Ballatore, F.; Bernardini, F.; Alfarano, M.; Della Rocca, D. G.; Severino, P.; Lavalle, C.; Francesco, F.; Frustaci, A. - 01g Articolo di rassegna (Review)

rivista: CARDIAC ELECTROPHYSIOLOGY CLINICS (Amsterdam : Elsevier) pp. 53-62 - issn: 1877-9182 - wos: (0) - scopus: 2-s2.0-85123711777 (21)

11573/1663564 - 2022 - A proposed strategy for anticoagulation therapy in noncompaction cardiomyopathy

Chimenti, Cristina; Lavalle, Carlo; Magnocavallo, Michele; Alfarano, Maria; Mariani, Marco Valerio; Bernardini, Federico; Della Rocca, Domenico Giovanni; Galardo, Gioacchino; Severino, Paolo; Di Lullo, Luca; Miraldi, Fabio; Fedele, Francesco; Frustaci, Andrea - 01g Articolo di rassegna (Review)

rivista: ESC HEART FAILURE ([Oxford] : published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology, 2014-) pp. 241-250 - issn: 2055-5822 - wos: WOS:000750055100001 (27) - scopus: 2-s2.0-85121382340 (25)

11573/1668112 - 2022 - Downregulation of mannose-6-phosphate receptors in fabry dsease cardiomyopathy: a potential target for enzyme therapy enhancement

Frustaci, Andrea; Verardo, Romina Annita; Scialla, Rossella; Bagnato, Giulia; Verardo, Margherita; Alfarano, Maria; Russo, Matteo Antonio - 01a Articolo in rivista

rivista: JOURNAL OF CLINICAL MEDICINE (MDPI Publishing, Basel, Switzerland) pp. 1-14 - issn: 2077-0383 - wos: WOS:000858256600001 (5) - scopus: 2-s2.0-85138741883 (5)

11573/1668110 - 2022 - Removal of cardiac AL-amyloid with positive remodeling of cardiomyocytes and of restrictive cardiomyopathy

Frustaci, Andrea; Verardo, Romina; Galea, Nicola; Alfarano, Maria; Sansone, Luigi; Russo, Matteo Antonio; Chimenti, Cristina - 01i Case report

rivista: ESC HEART FAILURE ([Oxford] : published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology, 2014-) pp. 4330-4334 - issn: 2055-5822 - wos: WOS:000849603400001 (0) - scopus: 2-s2.0-85137374309 (0)

11573/1549159 - 2021 - False-positive bone scintigraphy denoting transthyretin amyloid in elderly hypertrophic cardiomyopathy

Chimenti, Cristina; Alfarano, Maria; Maestrini, Viviana; Galea, Nicola; De Vincentis, Giuseppe; Verardo, Romina; Fedele, Francesco; Frustaci, Andrea - 01i Case report

rivista: ESC HEART FAILURE ([Oxford] : published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology, 2014-) pp. - - issn: 2055-5822 - wos: WOS:000653837600001 (11) - scopus: 2-s2.0-85106262713 (11)

11573/1612835 - 2021 - Myocardial aldosterone receptor and aquaporin 1 up-regulation is associated with cardiomyocyte remodeling in human heart failure

Frustaci, A.; Letizia, C.; Chimenti, C.; Verardo, R.; Alfarano, M.; Scialla, R.; Bagnato, G.; Miraldi, F.; Sansone, L.; Russo, M. A. - 01a Articolo in rivista

rivista: JOURNAL OF CLINICAL MEDICINE (MDPI Publishing, Basel, Switzerland) pp. - - issn: 2077-0383 - wos: WOS:000718542900001 (6) - scopus: 2-s2.0-85117474298 (5)

11573/1476410 - 2021 - Myocarditis-associated necrotizing coronary vasculitis: incidence, cause, and outcome

Frustaci, Andrea; Alfarano, Maria; Verardo, Romina Annita; Agrati, Chiara; Casetti, Rita; Miraldi, Fabio; Galea, Nicola; Letizia, Claudio; Chimenti, Cristina - 01a Articolo in rivista

rivista: EUROPEAN HEART JOURNAL (Oxford : Oxford University Press United Kingdom: Harcourt Publishers Limitedinternational.com, Fax: 011 44 20 83085876) pp. 1609-1617 - issn: 0195-668X - wos: WOS:000606106301202 (2) - scopus: 2-s2.0-85105760980 (8)

11573/1682297 - 2021 - Pemphigus-associated cardiomyopathy: report of autoimmune myocarditis and review of literature

Frustaci, Andrea; Francone, Marco; Verardo, Romina; Scialla, Rossella; Bagnato, Giulia; Alfarano, Maria; Chimenti, Cristina; Frustaci, Emanuela; Sansone, Luigi; Russo, Matteo - 01g Articolo di rassegna (Review)

rivista: ESC HEART FAILURE ([Oxford] : published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology, 2014-) pp. 3690-3695 - issn: 2055-5822 - wos: WOS:000688170600001 (2) - scopus: 2-s2.0-85113317400 (2)

11573/1460068 - 2020 - Myocarditis and intramural coronary vasculitis in polyarteritis nodosa: an unusual treatable form of heart failure

Chimenti, C.; Alfarano, M.; Toto, F.; Fanisio, F.; Verardo, R.; Galea, N.; Agati, L.; Frustaci, A. - 01i Case report

rivista: ESC HEART FAILURE ([Oxford] : published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology, 2014-) pp. 4357-4360 - issn: 2055-5822 - wos: WOS:000581098700001 (3) - scopus: 2-s2.0-85093506318 (2)

11573/1412990 - 2020 - Undiagnosed fabry disease. the importance of screening for fabry disease before transcutaneous patent foramen ovale closure in a young patient with cryptogenic stroke

Chimenti, Cristina; Alfarano, Maria; Galea, Nicola; Verardo, Romina; Grande, Claudia; Frustaci, Andrea - 01i Case report

rivista: JOURNAL OF CARDIOVASCULAR MEDICINE (Lippincott Williams & Wilkins) pp. 711-713 - issn: 1558-2027 - wos: WOS:000561261800015 (0) - scopus: 2-s2.0-85089126719 (0)

11573/1458776 - 2020 - Kappa-light chain amyloid overlapping hypertrophic cardiomyopathy with myocardial noncompactiony

Frustaci, A.; Galea, N.; Verardo, R.; Francone, M.; Alfarano, M.; Russo, M. A.; Chimenti, C. - 01a Articolo in rivista

rivista: CIRCULATION. CARDIOVASCULAR IMAGING (Philadelphia, PA : Lippincott Williams & Wilkins) pp. 1-4 - issn: 1942-0080 - wos: WOS:000561883600009 (3) - scopus: 2-s2.0-85087383721 (4)

11573/1354034 - 2020 - Heart failure from gouty myocarditis: a case report

Frustaci, Andrea; Russo, Matteo Antonio; Sansone, Luigi; Francone, Marco; Verardo, Romina; Grande, Claudia; Alfarano, Maria; Chimenti, Cristina - 01i Case report

rivista: ANNALS OF INTERNAL MEDICINE ([Philadelphia etc.]: [American College of Physicians]) pp. 363-365 - issn: 0003-4819 - wos: WOS:000520159500014 (5) - scopus: 2-s2.0-85082137222 (6)

11573/1276067 - 2018 - Immune-mediated myocarditis in fabry disease cardiomyopathy

Frustaci, Andrea; Verardo, Romina; Grande, Claudia; Galea, Nicola; Piselli, Pierluca; Carbone, Iacopo; Alfarano, Maria; Russo, Matteo Antonio; Chimenti, Cristina - 01a Articolo in rivista

rivista: JOURNAL OF THE AMERICAN HEART ASSOCIATION. CARDIOVASCULAR AND CEREBROVASCULAR DISEASE (Oxford: Wiley-Blackwell) pp. - - issn: 2047-9980 - wos: WOS:000452804600013 (46) - scopus: 2-s2.0-85054498547 (50)

11573/1029375 - 2017 - Immune-mediated myocarditis in fabry disease cardiomyopathy

Frustaci, Andrea; Verardo, Romina; Grande, Claudia; Galea, Nicola; Carbone, Iacopo; Alfarano, Maria; Russo, Matteo Antonio; Chimenti, Cristina - 04d Abstract in atti di convegno

rivista: EUROPEAN JOURNAL OF HEART FAILURE (ELSEVIER SCIENCE BV, PO BOX 211, AMSTERDAM, NETHERLANDS, 1000 AE) pp. 258-258 - issn: 1388-9842 - wos: (0) - scopus: (0)

libro: European journal of heart failure - ()

11573/1029415 - 2017 - Immune mediated myocarditis in Fabry disease cardiomyopathy

Frustaci, Andrea; Verardo, Romina; Grande, Claudia; Galea, Nicola; Carbone, Jacopo; Alfarano, Maria; Russo, Matteo Antonio; Chimenti, Cristina - 04d Abstract in atti di convegno

libro: Molecular genetics and Metabolism - ()

11573/1029440 - 2016 - Myocardial expression of Toll-like receptor 4 predicts the response to immunosuppressive therapy in patients with virus negative inflammatory cardiomyopathy

Chimenti, C; Verardo, R; Scopelliti, F; Grande, C; Alfarano, M; Petrosillo, N; Fedele, F; Frustaci, A. - 04d Abstract in atti di convegno

rivista: EUROPEAN HEART JOURNAL (Oxford : Oxford University Press United Kingdom: Harcourt Publishers Limitedinternational.com, Fax: 011 44 20 83085876) pp. 846-846 - issn: 0195-668X - wos: WOS:000383869504190 (0) - scopus: (0)

libro: European Heart Journal - ()