A5059284373- Cardiomyopathy and Myosin Studies
- Cardiac electrophysiology and arrhythmias
- Neuroscience and Neural Engineering
- Cardiovascular Effects of Exercise
- Cardiovascular Function and Risk Factors
- Photoreceptor and optogenetics research
- Muscle Physiology and Disorders
- Ion channel regulation and function
- Congenital heart defects research
- Neural dynamics and brain function
- Tissue Engineering and Regenerative Medicine
- Advanced Fluorescence Microscopy Techniques
- Viral Infections and Immunology Research
- Pluripotent Stem Cells Research
- Advanced Materials and Mechanics
- Electrospun Nanofibers in Biomedical Applications
- Cellular Mechanics and Interactions
- Advanced Sensor and Energy Harvesting Materials
- 3D Printing in Biomedical Research
- Electrochemical Analysis and Applications
- Cardiac Arrhythmias and Treatments
- EEG and Brain-Computer Interfaces
- Cardiac Structural Anomalies and Repair
- Adipose Tissue and Metabolism
- Photosynthetic Processes and Mechanisms
University of Florence
2015-2024
Azienda Ospedaliero-Universitaria Careggi
2010-2022
National Research Council
2019
Istituto Nazionale di Ricerca Metrologica
2019
Gilead Sciences (United States)
2012-2017
University of Arizona
2014-2017
Imperial College London
2012-2016
King's College London
2016
Centro Cardiologico Monzino
2016
Institute of Experimental Cardiology
2016
Background— Hypertrophic cardiomyopathy (HCM), the most common mendelian heart disorder, remains an orphan of disease-specific pharmacological treatment because limited understanding cellular mechanisms underlying arrhythmogenicity and diastolic dysfunction. Methods Results— We assessed electromechanical profile cardiomyocytes from 26 HCM patients undergoing myectomy compared with those nonfailing nonhypertrophic surgical by performing patch-clamp intracellular Ca 2+ (Ca i ) studies....
Mild hypertrophy but increased arrhythmic risk characterizes the stereotypic phenotype proposed for hypertrophic cardiomyopathy (HCM) caused by thin-filament mutations. However, whether such clinical profile is different from more prevalent thick-filament–associated disease unresolved. This study aimed to assess features and outcomes in a large cohort of patients with HCM associated mutations compared thick-filament HCM. Adult (age >18 years), 80 150 mutations, were followed an average 4.5...
Abstract Current rescue therapies for life-threatening arrhythmias ignore the pathological electro-anatomical substrate and base their efficacy on a generalized electrical discharge. Here, we developed an all-optical platform to examine less invasive defibrillation strategies. An ultrafast wide-field macroscope was optically map action potential propagation with red-shifted voltage sensitive dye in whole mouse hearts. The implemented random-access scanning head capable of drawing...
Background— Current therapies are ineffective in preventing the development of cardiac phenotype young carriers mutations associated with hypertrophic cardiomyopathy (HCM). Ranolazine, a late Na + current blocker, reduced electromechanical dysfunction human HCM myocardium vitro. Methods and Results— To test whether long-term treatment prevents vivo, transgenic mice harboring R92Q troponin-T mutation wild-type littermates received an oral lifelong ranolazine were compared age-matched...
The plasma membrane of cardiac myocytes presents complex invaginations known as the transverse-axial tubular system (TATS). Despite TATS's crucial role in excitation-contraction coupling and morphological alterations found pathological settings, electrical activity has never been directly investigated remodeled networks. Here we develop an ultrafast random access multiphoton microscope that, combination with a customly synthesized voltage-sensitive dye, is used to simultaneously measure...
Significance The plasma membrane of cardiac myocytes contains complex invaginations known as transverse tubules (T-tubules). In heart failure, T-tubule loss is a major contributor to Ca 2+ transient abnormalities, leading weaker and slower contraction. Current therapeutic strategies are often based on attempts accelerate transients. Here, we demonstrate that T-tubular represents just one way by which dysfunction leads asynchronous release across the myocyte. fact, report defects in...
In cardiomyocytes from patients with hypertrophic cardiomyopathy, mechanical dysfunction and arrhythmogenicity are caused by mutation-driven changes in myofilament function combined excitation-contraction (E-C) coupling abnormalities related to adverse remodeling. Whether or E-C alterations more relevant disease development is unknown. Here, we aim investigate whether the relative roles of remodeling determining cardiomyopathy phenotype mutation specific.Two mouse models carrying R92Q E163R...
Disopyramide is effective and safe in patients with obstructive hypertrophic cardiomyopathy. However, its cellular molecular mechanisms of action are unknown. We tested disopyramide cardiomyocytes from the septum surgical myectomy patients: inhibits multiple ion channels, leading to lower Ca transients force, shortens potentials, thus reducing arrhythmias. The electrophysiological profile explains efficient reduction outflow gradients but also limited prolongation QT interval absence...
Hypertrophic cardiomyopathy (HCM) is the most common mendelian heart disease, with a prevalence of 1/500. HCM primary cause sudden death, due to an heightened risk ventricular tachyarrhythmias that often occur in young asymptomatic patients. can slowly progress towards failure, either preserved or reduced ejection fraction, worsening diastolic function. Accumulation intra-myocardial fibrosis and replacement scars underlies failure progression represents substrate for sustained arrhythmias...
Rationale: Despite major advances in cardiovascular medicine, heart disease remains a leading cause of death worldwide. However, the field tissue engineering has been growing exponentially last decade and restoring functionality is now an affordable target; yet, new materials are still needed for effectively provide rapid long-lasting interventions. Liquid crystalline elastomers (LCEs) biocompatible polymers able to reversibly change shape response given stimulus generate movement. Once...
Cardiac action potential (AP) shape and propagation are regulated by several key dynamic factors such as ion channel recovery intracellular Ca2+ cycling. Experimental methods for manipulating AP electrical dynamics commonly use inhibitors that lack spatial temporal specificity. In this work, we propose an approach based on optogenetics to manipulate cardiac activity employing a light-modulated depolarizing current with intensities too low elicit APs (sub-threshold illumination), but...
Background: The pathogenesis of MYBPC3 -associated hypertrophic cardiomyopathy (HCM) is still unresolved. In our HCM patient cohort, a large and well-characterized population carrying the :c772G>A variant (p.Glu258Lys, E258K) provides unique opportunity to study basic mechanisms -HCM with comprehensive translational approach. Methods: We collected clinical genetic data from 93 patients variant. Functional perturbations were investigated using different biophysical techniques in left...
Abstract The communication reports the use of liquid crystalline networks (LCNs) for engineering tissue cultures with human cells. Their ability as cell scaffolds different lines is demonstrated. Preliminary assessments material biocompatibility are performed on dermal fibroblasts and murine muscle cells (C2C12), demonstrating that coatings or other treatments not needed to acrylate‐based materials support. Moreover, it found adherent C2C12 undergo differentiation, forming multinucleated...
In 30-40% of hypertrophic cardiomyopathy (HCM) patients, symptomatic left ventricular (LV) outflow gradients develop only during exercise due to catecholamine-induced LV hypercontractility (inducible obstruction). Negative inotropic pharmacological options are limited β-blockers or disopyramide, with low efficacy and tolerability. We assessed the potential late sodium current (INaL )-inhibitors treat inducible obstruction in HCM.The electrophysiological mechanical responses β-adrenoceptor...
Abstract Aims Heart failure invariably affects patients with various forms of muscular dystrophy (MD), but the onset and molecular sequelae altered structure function resulting from full-length dystrophin (Dp427) deficiency in MD heart tissue are poorly understood. To better understand role cardiomyocyte development earliest phase Duchenne (DMD) cardiomyopathy, we studied human cardiomyocytes differentiated induced pluripotent stem cells (hiPSC-CMs) obtained urine a DMD patient. Methods...
Mavacamten (MYK-461) is a small-molecule allosteric inhibitor of sarcomeric myosins being used in preclinical/clinical trials for hypertrophic cardiomyopathy treatment. A better understanding its impact on force generation intact or skinned striated muscle preparations, especially human cardiac muscle, has been hindered by diffusional barriers. These limitations have overcome mechanical experiments using myofibrils subject to perturbations the contractile environment sudden solution changes....
Action potential–driven Ca2+ currents from the transverse tubules (t-tubules) trigger synchronous release sarcoplasmic reticulum of cardiomyocytes. Loss t-tubules has been reported in cardiac diseases, including heart failure, but effect uncoupling sarcolemma on muscle mechanics remains largely unknown. We dissected intact rat right ventricular trabeculae and compared force, sarcomere length, intracellular control with which were uncoupled plasma membrane by formamide-induced osmotic shock...
Abnormalities of cardiomyocyte Ca2+ homeostasis and excitation–contraction (E–C) coupling are early events in the pathogenesis hypertrophic cardiomyopathy (HCM) concomitant determinants diastolic dysfunction arrhythmias typical disease. T-tubule remodelling has been reported to occur HCM but little is known about its role E–C alterations HCM. Here, electro-mechanical associated investigated Δ160E cTnT mouse model that expresses a clinically-relevant mutation. Contractile function intact...
Although optogenetics has clearly demonstrated the feasibility of cardiac manipulation, current optical stimulation strategies lack capability to react acutely ongoing wave dynamics. Here, we developed an all-optical platform monitor and control electrical activity in real-time. The methodology was applied restore normal after atrioventricular block manipulate intraventricular propagation wavefront. closed-loop approach also simulate a re-entrant circuit across ventricle. development this...