A5059236440- Cardiomyopathy and Myosin Studies
- Cardiovascular Effects of Exercise
- Tissue Engineering and Regenerative Medicine
- Congenital heart defects research
- Cardiac electrophysiology and arrhythmias
- Cardiovascular Function and Risk Factors
- Muscle Physiology and Disorders
- Pluripotent Stem Cells Research
- 3D Printing in Biomedical Research
- Neuroscience and Neural Engineering
- Viral Infections and Immunology Research
- Advanced Materials and Mechanics
- Electrospun Nanofibers in Biomedical Applications
- Cellular Mechanics and Interactions
- Advanced Sensor and Energy Harvesting Materials
- Ion channel regulation and function
- Cardiac Arrhythmias and Treatments
- Soft Robotics and Applications
- Additive Manufacturing and 3D Printing Technologies
University of Florence
2015-2024
Azienda Ospedaliero-Universitaria Careggi
2017
Gilead Sciences (United States)
2017
University of Arizona
2017
University of Washington
2015
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...
Tension production and contractile properties are poorly characterized aspects of excitation-contraction coupling human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Previous approaches have been limited due to the small size structural immaturity early-stage hiPSC-CMs. We developed a substrate nanopatterning approach produce hiPSC-CMs in culture with adult-like dimensions, T-tubule-like structures, aligned myofibrils. then isolated myofibrils from measured tension...
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...
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...
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...
The contractile properties of human fetal cardiac muscle have not been previously studied. Small-scale approaches such as isolated myofibril and protein biomechanical assays allow study activation relaxation kinetics under well-controlled conditions. We examined the myofibrils myosin across gestational age 59-134 days. Human low force slow that increase during time period studied, kinetic changes may result from structural maturation in isoform expression. Understanding course structure can...
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...
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...
Cardiomyocytes from human induced pluripotent stem cells (hiPSC-CMs) are the most promising source with preserved genetic background of healthy individuals or patients. This study aimed to establish a systematic procedure for exploring development hiPSC-CM functional output predict cardiomyopathy outcomes and identify molecular targets therapy. Biomimetic substrates microtopography physiological stiffness can overcome immaturity function. We have developed custom-made apparatus simultaneous...
Cardiomyopathy is currently the leading cause of death for patients with Duchenne muscular dystrophy (DMD), a severe neuromuscular disorder affecting young boys. Animal models have provided insight into mechanisms by which dystrophin protein deficiency causes cardiomyopathy, but there remains need to develop human DMD validate pathogenic and identify therapeutic targets. Here, we developed engineered heart tissues (EHTs) from CRISPR-edited, induced pluripotent stem cell-derived...
Myofibril based mechanical studies allow evaluation of sarcomeric protein function. We describe a novel method obtaining myofibrils from primary cardiomyocyte culture. Adult rat ventricular myocytes (ARVMs) were obtained by enzymatic digestion and maintained in serum free condition. ARVMs homogenized relaxing solution (pCa 9.0) with 20% sucrose, myofibril suspension was made. Myofibrils Ca2+-activated relaxed at 15°C. Results ARVM compared to tissue skinned Triton X-100. At maximal...
We describe the development of a bioink to bioprint human induced pluripotent stem cells (hiPSCs) for possible cardiac tissue engineering using gelatin methacrylate (GelMA)-based hydrogel. While previous studies have shown that GelMA at low concentration (5%
Ryanodine receptor (RyR2) is the major Ca2+ channel of cardiac sarcoplasmic reticulum (SR) and plays a crucial role in generation myocardial force. Changes RyR2 gating properties resulting increases its open probability (Po) are associated with leakage from SR arrhythmias; however, effects dysfunction on contractility unknown. Here, we investigated possibility that mutation catecholaminergic polymorphic ventricular tachycardia, R4496C, affects contractile function atrial myocardium. We...
Abstract Full muscle relaxation happens when [Ca 2+ ] falls below the threshold for force activation. Several experimental models, from whole organs and intact down to skinned fibers, have been used explore cascade of kinetic events leading mechanical relaxation. The use single myofibrils together with fast solution switching techniques, has provided new information about role cross-bridge (CB) dissociation in time course isometric decay. Myofibril’s is biphasic starting a slow seemingly...
Atrial dilation and atrial fibrillation (AF) are common in Hypertrophic CardioMyopathy (HCM) patients associated with a worsening of prognosis. The pathogenesis myopathy HCM remains poorly investigated no specific association genotype has been identified. By re-analysis our cohort thin-filament (Coppini et al. 2014) AF was identified 10% sporadic mutations the cardiac Troponin T gene ( TNNT2 ), while occurrence much higher (25–75%) carrying “hot-spot” mutations. To determine molecular basis...
Cardiomyocytes differentiated from human induced Pluripotent Stem Cells (hiPSC- CMs) are a unique source for modelling inherited cardiomyopathies. In particular, the possibility of observing maturation processes in simple culture dish opens novel perspectives study early-disease defects caused by genetic mutations before onset clinical manifestations. For instance, calcium handling abnormalities considered as leading cause cardiomyocyte dysfunction several genetic-based dilated...
Abstract Aims Ventricular cardiomyocytes from hypertrophic cardiomyopathy (HCM) patient hearts show prolonged action potential duration (APD), impaired intracellular Ca2+ homeostasis and abnormal electrical response to beta -adrenergic stimulation. We sought determine whether this behaviour is associated with changes of repolarization during exercise worsening diastolic function, ultimately explaining the intolerance experienced by some patients without obstruction. Methods results...