The Experts below are selected from a list of 82014 Experts worldwide ranked by ideXlab platform
Raffaella Bloise - One of the best experts on this subject based on the ideXlab platform.
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camkii inhibition rectifies arrhythmic phenotype in a Patient Specific Model of catecholaminergic polymorphic ventricular tachycardia
Cell Death and Disease, 2013Co-Authors: E Di Pasquale, Francesco Lodola, Marco Denegri, Hiroko Nakahama, Michele Miragoli, J Avelinocruz, M Buonocore, P Portararo, Raffaella BloiseAbstract:CaMKII inhibition rectifies arrhythmic phenotype in a Patient-Specific Model of catecholaminergic polymorphic ventricular tachycardia
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CaMKII inhibition rectifies arrhythmic phenotype in a Patient-Specific Model of catecholaminergic polymorphic ventricular tachycardia
Cell Death & Disease, 2013Co-Authors: E Di Pasquale, Francesco Lodola, Marco Denegri, Michele Miragoli, M Buonocore, P Portararo, Raffaella Bloise, J E Avelino-cruz, H Nakahama, C NapolitanoAbstract:Induced pluripotent stem cells (iPSC) offer a unique opportunity for developmental studies, disease Modeling and regenerative medicine approaches in humans. The aim of our study was to create an in vitro ‘Patient-Specific cell-based system’ that could facilitate the screening of new therapeutic molecules for the treatment of catecholaminergic polymorphic ventricular tachycardia (CPVT), an inherited form of fatal arrhythmia. Here, we report the development of a cardiac Model of CPVT through the generation of iPSC from a CPVT Patient carrying a heterozygous mutation in the cardiac ryanodine receptor gene ( RyR2 ) and their subsequent differentiation into cardiomyocytes (CMs). Whole-cell patch-clamp and intracellular electrical recordings of spontaneously beating cells revealed the presence of delayed afterdepolarizations (DADs) in CPVT-CMs, both in resting conditions and after β -adrenergic stimulation, resembling the cardiac phenotype of the Patients. Furthermore, treatment with KN-93 (2-[ N -(2-hydroxyethyl)]- N -(4methoxybenzenesulfonyl)]amino- N -(4-chlorocinnamyl)- N -methylbenzylamine), an antiarrhythmic drug that inhibits Ca^2+/calmodulin-dependent serine–threonine protein kinase II (CaMKII), drastically reduced the presence of DADs in CVPT-CMs, rescuing the arrhythmic phenotype induced by catecholaminergic stress. In addition, intracellular calcium transient measurements on 3D beating clusters by fast resolution optical mapping showed that CPVT clusters developed multiple calcium transients, whereas in the wild-type clusters, only single initiations were detected. Such instability is aggravated in the presence of isoproterenol and is attenuated by KN-93. As seen in our RyR2 knock-in CPVT mice, the antiarrhythmic effect of KN-93 is confirmed in these human iPSC-derived cardiac cells, supporting the role of this in vitro system for drug screening and optimization of clinical treatment strategies.
Michele Miragoli - One of the best experts on this subject based on the ideXlab platform.
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camkii inhibition rectifies arrhythmic phenotype in a Patient Specific Model of catecholaminergic polymorphic ventricular tachycardia
Cell Death and Disease, 2013Co-Authors: E Di Pasquale, Francesco Lodola, Marco Denegri, Hiroko Nakahama, Michele Miragoli, J Avelinocruz, M Buonocore, P Portararo, Raffaella BloiseAbstract:CaMKII inhibition rectifies arrhythmic phenotype in a Patient-Specific Model of catecholaminergic polymorphic ventricular tachycardia
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CaMKII inhibition rectifies arrhythmic phenotype in a Patient-Specific Model of catecholaminergic polymorphic ventricular tachycardia
Cell Death & Disease, 2013Co-Authors: E Di Pasquale, Francesco Lodola, Marco Denegri, Michele Miragoli, M Buonocore, P Portararo, Raffaella Bloise, J E Avelino-cruz, H Nakahama, C NapolitanoAbstract:Induced pluripotent stem cells (iPSC) offer a unique opportunity for developmental studies, disease Modeling and regenerative medicine approaches in humans. The aim of our study was to create an in vitro ‘Patient-Specific cell-based system’ that could facilitate the screening of new therapeutic molecules for the treatment of catecholaminergic polymorphic ventricular tachycardia (CPVT), an inherited form of fatal arrhythmia. Here, we report the development of a cardiac Model of CPVT through the generation of iPSC from a CPVT Patient carrying a heterozygous mutation in the cardiac ryanodine receptor gene ( RyR2 ) and their subsequent differentiation into cardiomyocytes (CMs). Whole-cell patch-clamp and intracellular electrical recordings of spontaneously beating cells revealed the presence of delayed afterdepolarizations (DADs) in CPVT-CMs, both in resting conditions and after β -adrenergic stimulation, resembling the cardiac phenotype of the Patients. Furthermore, treatment with KN-93 (2-[ N -(2-hydroxyethyl)]- N -(4methoxybenzenesulfonyl)]amino- N -(4-chlorocinnamyl)- N -methylbenzylamine), an antiarrhythmic drug that inhibits Ca^2+/calmodulin-dependent serine–threonine protein kinase II (CaMKII), drastically reduced the presence of DADs in CVPT-CMs, rescuing the arrhythmic phenotype induced by catecholaminergic stress. In addition, intracellular calcium transient measurements on 3D beating clusters by fast resolution optical mapping showed that CPVT clusters developed multiple calcium transients, whereas in the wild-type clusters, only single initiations were detected. Such instability is aggravated in the presence of isoproterenol and is attenuated by KN-93. As seen in our RyR2 knock-in CPVT mice, the antiarrhythmic effect of KN-93 is confirmed in these human iPSC-derived cardiac cells, supporting the role of this in vitro system for drug screening and optimization of clinical treatment strategies.
E Di Pasquale - One of the best experts on this subject based on the ideXlab platform.
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camkii inhibition rectifies arrhythmic phenotype in a Patient Specific Model of catecholaminergic polymorphic ventricular tachycardia
Cell Death and Disease, 2013Co-Authors: E Di Pasquale, Francesco Lodola, Marco Denegri, Hiroko Nakahama, Michele Miragoli, J Avelinocruz, M Buonocore, P Portararo, Raffaella BloiseAbstract:CaMKII inhibition rectifies arrhythmic phenotype in a Patient-Specific Model of catecholaminergic polymorphic ventricular tachycardia
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CaMKII inhibition rectifies arrhythmic phenotype in a Patient-Specific Model of catecholaminergic polymorphic ventricular tachycardia
Cell Death & Disease, 2013Co-Authors: E Di Pasquale, Francesco Lodola, Marco Denegri, Michele Miragoli, M Buonocore, P Portararo, Raffaella Bloise, J E Avelino-cruz, H Nakahama, C NapolitanoAbstract:Induced pluripotent stem cells (iPSC) offer a unique opportunity for developmental studies, disease Modeling and regenerative medicine approaches in humans. The aim of our study was to create an in vitro ‘Patient-Specific cell-based system’ that could facilitate the screening of new therapeutic molecules for the treatment of catecholaminergic polymorphic ventricular tachycardia (CPVT), an inherited form of fatal arrhythmia. Here, we report the development of a cardiac Model of CPVT through the generation of iPSC from a CPVT Patient carrying a heterozygous mutation in the cardiac ryanodine receptor gene ( RyR2 ) and their subsequent differentiation into cardiomyocytes (CMs). Whole-cell patch-clamp and intracellular electrical recordings of spontaneously beating cells revealed the presence of delayed afterdepolarizations (DADs) in CPVT-CMs, both in resting conditions and after β -adrenergic stimulation, resembling the cardiac phenotype of the Patients. Furthermore, treatment with KN-93 (2-[ N -(2-hydroxyethyl)]- N -(4methoxybenzenesulfonyl)]amino- N -(4-chlorocinnamyl)- N -methylbenzylamine), an antiarrhythmic drug that inhibits Ca^2+/calmodulin-dependent serine–threonine protein kinase II (CaMKII), drastically reduced the presence of DADs in CVPT-CMs, rescuing the arrhythmic phenotype induced by catecholaminergic stress. In addition, intracellular calcium transient measurements on 3D beating clusters by fast resolution optical mapping showed that CPVT clusters developed multiple calcium transients, whereas in the wild-type clusters, only single initiations were detected. Such instability is aggravated in the presence of isoproterenol and is attenuated by KN-93. As seen in our RyR2 knock-in CPVT mice, the antiarrhythmic effect of KN-93 is confirmed in these human iPSC-derived cardiac cells, supporting the role of this in vitro system for drug screening and optimization of clinical treatment strategies.
Francesco Lodola - One of the best experts on this subject based on the ideXlab platform.
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Adeno-associated virus-mediated CASQ2 delivery rescues phenotypic alterations in a Patient-Specific Model of recessive catecholaminergic polymorphic ventricular tachycardia
Cell Death & Disease, 2016Co-Authors: Francesco Lodola, Diego Morone, Marco Denegri, Rossana Bongianino, Hiroko Nakahama, Lucia Rutigliano, Rosanna Gosetti, Giulia Rizzo, Alessandra Vollero, Michelangelo BuonocoreAbstract:Catecholaminergic Polymorphic Ventricular Tachycardia type 2 (CPVT2) is a highly lethal recessive arrhythmogenic disease caused by mutations in the calsequestrin-2 ( CASQ2 ) gene. We have previously demonstrated that viral transfer of the wild-type (WT) CASQ2 gene prevents the development of CPVT2 in a genetically induced mouse Model of the disease homozygous carrier of the R33Q mutation. In the present study, we investigated the efficacy of the virally mediated gene therapy in cardiomyocytes (CMs) differentiated from induced pluripotent stem cells (iPSCs) obtained from a Patient carrying the homozygous CASQ2-G112+5X mutation. To this end, we infected cells with an Adeno-Associated Viral vector serotype 9 (AAV9) encoding the human CASQ2 gene (AAV9-h CASQ2 ). Administration of the human WT CASQ2 gene was capable and sufficient to restore the physiological expression of calsequestrin-2 protein and to rescue functional defects of the Patient-Specific iPSC-derived CMs. Indeed, after viral gene transfer, we observed a remarkable decrease in the percentage of delayed afterdepolarizations (DADs) developed by the diseased CMs upon adrenergic stimulation, the calcium transient amplitude was re-established and the density and duration of calcium sparks were normalized. We therefore demonstrate the efficacy of the AAV9-mediated gene replacement therapy for CPVT2 in a human cardiac-Specific Model system, supporting the view that the gene-therapy tested is curative in Models with different human mutations of CPVT.
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camkii inhibition rectifies arrhythmic phenotype in a Patient Specific Model of catecholaminergic polymorphic ventricular tachycardia
Cell Death and Disease, 2013Co-Authors: E Di Pasquale, Francesco Lodola, Marco Denegri, Hiroko Nakahama, Michele Miragoli, J Avelinocruz, M Buonocore, P Portararo, Raffaella BloiseAbstract:CaMKII inhibition rectifies arrhythmic phenotype in a Patient-Specific Model of catecholaminergic polymorphic ventricular tachycardia
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CaMKII inhibition rectifies arrhythmic phenotype in a Patient-Specific Model of catecholaminergic polymorphic ventricular tachycardia
Cell Death & Disease, 2013Co-Authors: E Di Pasquale, Francesco Lodola, Marco Denegri, Michele Miragoli, M Buonocore, P Portararo, Raffaella Bloise, J E Avelino-cruz, H Nakahama, C NapolitanoAbstract:Induced pluripotent stem cells (iPSC) offer a unique opportunity for developmental studies, disease Modeling and regenerative medicine approaches in humans. The aim of our study was to create an in vitro ‘Patient-Specific cell-based system’ that could facilitate the screening of new therapeutic molecules for the treatment of catecholaminergic polymorphic ventricular tachycardia (CPVT), an inherited form of fatal arrhythmia. Here, we report the development of a cardiac Model of CPVT through the generation of iPSC from a CPVT Patient carrying a heterozygous mutation in the cardiac ryanodine receptor gene ( RyR2 ) and their subsequent differentiation into cardiomyocytes (CMs). Whole-cell patch-clamp and intracellular electrical recordings of spontaneously beating cells revealed the presence of delayed afterdepolarizations (DADs) in CPVT-CMs, both in resting conditions and after β -adrenergic stimulation, resembling the cardiac phenotype of the Patients. Furthermore, treatment with KN-93 (2-[ N -(2-hydroxyethyl)]- N -(4methoxybenzenesulfonyl)]amino- N -(4-chlorocinnamyl)- N -methylbenzylamine), an antiarrhythmic drug that inhibits Ca^2+/calmodulin-dependent serine–threonine protein kinase II (CaMKII), drastically reduced the presence of DADs in CVPT-CMs, rescuing the arrhythmic phenotype induced by catecholaminergic stress. In addition, intracellular calcium transient measurements on 3D beating clusters by fast resolution optical mapping showed that CPVT clusters developed multiple calcium transients, whereas in the wild-type clusters, only single initiations were detected. Such instability is aggravated in the presence of isoproterenol and is attenuated by KN-93. As seen in our RyR2 knock-in CPVT mice, the antiarrhythmic effect of KN-93 is confirmed in these human iPSC-derived cardiac cells, supporting the role of this in vitro system for drug screening and optimization of clinical treatment strategies.
Dorin Comaniciu - One of the best experts on this subject based on the ideXlab platform.
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complete valvular heart apparatus Model from 4d cardiac ct
Medical Image Analysis, 2012Co-Authors: Ingmar Voigt, Razvan Ioan Ionasec, Bogdan Georgescu, Yang Wang, Sasa Grbic, Dime Vitanovski, Nassir Navab, Dorin ComaniciuAbstract:Abstract The cardiac valvular apparatus, composed of the aortic, mitral, pulmonary and tricuspid valves, is an essential part of the anatomical, functional and hemodynamic characteristics of the heart and the cardiovascular system as a whole. Valvular heart diseases often involve multiple dysfunctions and require joint assessment and therapy of the valves. In this paper, we propose a complete and modular Patient-Specific Model of the cardiac valvular apparatus estimated from 4D cardiac CT data. A new constrained Multi-linear Shape Model (cMSM), conditioned by anatomical measurements, is introduced to represent the complex spatio-temporal variation of the heart valves. The cMSM is exploited within a learning-based framework to efficiently estimate the Patient-Specific valve parameters from cine images. Experiments on 64 4D cardiac CT studies demonstrate the performance and clinical potential of the proposed method. Our method enambles automatic quantitative evaluation of the complete valvular apparatus based on non-invasive imaging techniques. In conjunction with existent Patient-Specific chamber Models, the presented valvular Model enables personalized computation Modeling and realistic simulation of the entire cardiac system.
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Patient Specific Modelling of whole heart anatomy dynamics and haemodynamics from four dimensional cardiac ct images
Interface Focus, 2011Co-Authors: Viorel Mihalef, Puneet. Sharma, Ingmar Voigt, Razvan Ioan Ionasec, Bogdan Georgescu, Michael Suehling, Dorin ComaniciuAbstract:There is a growing need for Patient-Specific and holistic Modelling of the heart to support comprehensive disease assessment and intervention planning as well as prediction of therapeutic outcomes. We propose a Patient-Specific Model of the whole human heart, which integrates morphology, dynamics and haemodynamic parameters at the organ level. The Modelled cardiac structures are robustly estimated from four-dimensional cardiac computed tomography (CT), including all four chambers and valves as well as the ascending aorta and pulmonary artery. The Patient-Specific geometry serves as an input to a three-dimensional Navier–Stokes solver that derives realistic haemodynamics, constrained by the local anatomy, along the entire heart cycle. We evaluated our framework with various heart pathologies and the results correlate with relevant literature reports.
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complete valvular heart apparatus Model from 4d cardiac ct
Medical Image Computing and Computer-Assisted Intervention, 2010Co-Authors: Sasa Grbic, Ingmar Voigt, Razvan Ioan Ionasec, Bogdan Georgescu, Yang Wang, Dime Vitanovski, Nassir Navab, Dorin ComaniciuAbstract:The cardiac valvular apparatus, composed of the aortic, mitral, pulmonary and tricuspid valve, is an essential part of the anatomical, functional and hemodynamic mechanism of the heart and the cardiovascular system as a whole. Valvular heart diseases often involve multiple dysfunctions and require joint assessment and therapy of the valves. In this paper, we propose a complete and modular Patient-Specific Model of the cardiac valvular apparatus estimated from 4D cardiac CT data. A new constrained Multi-linear Shape Model (cMSM), conditioned by anatomical measurements, is introduced to represent the complex spatiotemporal variation of the heart valves. The cMSM is exploited within a learning-based framework to efficiently estimate the Patient-Specific valve parameters from cine images. Experiments on 64 4D cardiac CT studies demonstrate the performance and clinical potential of the proposed method. To the best of our knowledge, it is the first time cardiologists and cardiac surgeons can benefit from an automatic quantitative evaluation of the complete valvular apparatus based on non-invasive imaging techniques. In conjunction with existent Patient-Specific chamber Models, the presented valvular Model enables personalized computation Modeling and realistic simulation of the entire cardiac system.
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Patient-Specific Modeling of left heart anatomy, dynamics and hemodynamics from high resolution 4D CT
2010 IEEE International Symposium on Biomedical Imaging: From Nano to Macro, 2010Co-Authors: Viorel Mihalef, Razvan Ioan Ionasec, Bogdan Georgescu, Yang Wang, Yefeng Zheng, Dorin ComaniciuAbstract:There is a growing need for Patient-Specific cardiac Models for intervention planning, outcome prediction or assessment of cardiac disease progression. However, most of the recent work in cardiovascular simulation relies on generic heart Models built from at most one cardiac phase with simplified motion, driven by fluid dynamics equations. We propose to advance the state-of-the-art by exploiting a comprehensive, Patient-Specific left heart Model extracted from 4D Computed Tomography (CT) data. Explicit physiological constrains are captured in the Modeling of the left ventricle (including outflow tract), left atrium (including pulmonary veins), mitral valve, and aortic valve (including ascending aorta). By using this Patient-Specific Model as an input to a 3D Navier-Stokes solver we derive realistic hemodynamics, constrained by the local anatomy, along the entire heart cycle. We present a differential assessment of the flow dynamics corresponding to Specific heart conditions. The simulation results shed light upon the functional differences between one normal and two diseased hearts - one with a dilated aortic root and one with a bicuspid aortic valve.