Federica Giannetti

RESEARCH INTERESTS

Electrophysiology, Cell biology, Cardiac diseases, hiPSC, Arrhythmias

Scopus Publications

Rescue of loss-of-function long QT syndrome-associated mutations in K<inf>V</inf>7.1/KCNE1 by the endocannabinoid N-arachidonoyl-L-serine (ARA-S)
Irene Hiniesto‐Iñigo, Akshay Sridhar, Julien Louradour, Alicia De la Cruz, Siri Lundholm, Amaia Jauregi‐Miguel, Federica Giannetti, Luca Sala, Katja E. Odening, H. Peter Larsson,et al.
Wiley
AbstractBackground and PurposeCongenital long QT syndrome (LQTS) involves genetic mutations affecting ion channels, leading to a prolonged QT interval and increased risk of potentially lethal ventricular arrhythmias. Mutations in the genes encoding KV7.1/KCNE1 are the most frequent, with channel loss‐of‐function contributing to LQTS. The endocannabinoid N‐arachidonoyl‐L‐serine (ARA‐S) has been shown to facilitate activation of wild type KV7.1/KCNE1 channels and to counteract a prolonged QT interval in isolated guinea pig hearts. In this study, we examine the ability of ARA‐S to facilitate activation of LQTS‐associated mutations, in various regions of the channel, and hence to counteract loss‐of‐function.Experimental ApproachThe two‐electrode voltage clamp technique on Xenopus oocytes expressing human KV7.1/KCNE1 channels was used to investigate the effects of ARA‐S in 20 LQTS type 1‐associated mutations distributed across the channel. Thereafter, different electrophysiology was used to assess ARA‐S effects in mammalian cells.Key ResultsARA‐S enhanced the function of all mutated channels by shifting V50 and increasing current amplitude. However, the magnitude of effect varied, related to whether mutations were in one of the two putative ARA‐S binding sites on the channel as suggested by molecular dynamics simulations. ARA‐S displayed translational potential by facilitating channel opening in mammalian cells and shortening the action potential duration in cardiomyocytes.Conclusions and ImplicationsThis study demonstrates the rescuing capability of ARA‐S on a diverse set of LQTS mutants. These insights may aid in developing drug compounds using ARA‐S sites and mechanisms and guide interpretation of which LQTS mutants respond well to such compounds.


Therapeutic Efficacy of Mexiletine for Long QT Syndrome Type 2: Evidence from Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes, Transgenic Rabbits, and Patients
Lia Crotti, Raquel Neves, Federica Dagradi, Giulia Musu, Federica Giannetti, J. Martijn Bos, Miriam Barbieri, Paolo Cerea, Fulvio L.F. Giovenzana, Margherita Torchio,et al.
Ovid Technologies (Wolters Kluwer Health)
BACKGROUND: Despite major advances in the clinical management of long QT syndrome, some patients are not fully protected by beta-blocker therapy. Mexiletine is a well-known sodium channel blocker, with proven efficacy in patients with sodium channel–mediated long QT syndrome type 3. Our aim was to evaluate the efficacy of mexiletine in long QT syndrome type 2 (LQT2) using cardiomyocytes derived from patient-specific human induced pluripotent stem cells, a transgenic LQT2 rabbit model, and patients with LQT2. METHODS: Heart rate–corrected field potential duration, a surrogate for QTc, was measured in human induced pluripotent stem cells from 2 patients with LQT2 (KCNH2-p.A561V, KCNH2-p.R366X) before and after mexiletine using a multiwell multi-electrode array system. Action potential duration at 90% repolarization (APD 90 ) was evaluated in cardiomyocytes isolated from transgenic LQT2 rabbits (KCNH2-p.G628S) at baseline and after mexiletine application. Mexiletine was given to 96 patients with LQT2. Patients were defined as responders in the presence of a QTc shortening ≥40 ms. Antiarrhythmic efficacy of mexiletine was evaluated by a Poisson regression model. RESULTS: After acute treatment with mexiletine, human induced pluripotent stem cells from both patients with LQT2 showed a significant shortening of heart rate–corrected field potential duration compared with dimethyl sulfoxide control. In cardiomyocytes isolated from LQT2 rabbits, acute mexiletine significantly shortened APD 90 by 113 ms, indicating a strong mexiletine-mediated shortening across different LQT2 model systems. Mexiletine was given to 96 patients with LQT2 either chronically (n=60) or after the acute oral drug test (n=36): 65% of the patients taking mexiletine only chronically and 75% of the patients who performed the acute oral test were responders. There was a significant correlation between basal QTc and ∆QTc during the test ( r = −0.8; P &lt;0.001). The oral drug test correctly predicted long-term effect in 93% of the patients. Mexiletine reduced the mean yearly event rate from 0.10 (95% CI, 0.07–0.14) to 0.04 (95% CI, 0.02–0.08), with an incidence rate ratio of 0.40 (95% CI, 0.16–0.84), reflecting a 60% reduction in the event rate ( P =0.01). CONCLUSIONS: Mexiletine significantly shortens cardiac repolarization in LQT2 human induced pluripotent stem cells, in the LQT2 rabbit model, and in the majority of patients with LQT2. Furthermore, mexiletine showed antiarrhythmic efficacy. Mexiletine should therefore be considered a valid therapeutic option to be added to conventional therapies in higher-risk patients with LQT2.


Striatin knock out induces a gain of function of I<inf>Na</inf> and impaired Ca²⁺ handling in mESC-derived cardiomyocytes
P. Benzoni, M. Arici, F. Giannetti, A. Cospito, R. Prevostini, C. Volani, L. Fassina, M. D. Rosato‐Siri, A. Metallo, L. Gennaccaro,et al.
Wiley
AbstractAimStriatin (Strn) is a scaffold protein expressed in cardiomyocytes (CMs) and alteration of its expression are described in various cardiac diseases. However, the alteration underlying its pathogenicity have been poorly investigated.MethodsWe studied the role(s) of cardiac Strn gene (STRN) by comparing the functional properties of CMs, generated from Strn‐KO and isogenic WT mouse embryonic stem cell lines.ResultsThe spontaneous beating rate of Strn‐KO CMs was faster than WT cells, and this correlated with a larger fast INa conductance and no changes in If. Paced (2–8 Hz) Strn‐KO CMs showed prolonged action potential (AP) duration in comparison with WT CMs and this was not associated with changes in ICaL and IKr. Motion video tracking analysis highlighted an altered contraction in Strn‐KO CMs; this was associated with a global increase in intracellular Ca2+, caused by an enhanced late Na+ current density (INaL) and a reduced Na+/Ca2+ exchanger (NCX) activity and expression. Immunofluorescence analysis confirmed the higher Na+ channel expression and a more dynamic microtubule network in Strn‐KO CMs than in WT. Indeed, incubation of Strn‐KO CMs with the microtubule stabilizer taxol, induced a rescue (downregulation) of INa conductance toward WT levels.ConclusionLoss of STRN alters CMs electrical and contractile profiles and affects cell functionality by a disarrangement of Strn‐related multi‐protein complexes. This leads to impaired microtubules dynamics and Na+ channels trafficking to the plasma membrane, causing a global Na+ and Ca2+ enhancement.


Use of hiPSC-derived cardiomyocytes to study LQTS-variant specific proarrhythmic effects of drugs
Luca Sala, Aleksandr Khudiakov, Manuela Mura, Vladislav Leonov, Federica Giannetti, Lia Crotti, Massimiliano Gnecchi, and Peter J. Schwartz
Elsevier BV



A gain of function mutation in PITX2c gene linked to atrial fibrillation alters mitochondrial function and membrane excitability
Patrizia Benzoni, Lorenzo Da Dalt, Alessandro Cospito, Vera Popolizio, Federica Giannetti, Cristina Ruberti, Mirko Baruscotti, Annalisa Bucchi, Giuseppe Danilo Norata, and Andrea Barbuti
Elsevier BV



Lack of the transcription factor Nfix causes tachycardia in mice sinus node and rats neonatal cardiomyocytes
Sara Landi, Federica Giannetti, Patrizia Benzoni, Giulia Campostrini, Giuliana Rossi, Chiara Piantoni, Giorgia Bertoli, Chiara Bonfanti, Luca Carnevali, Annalisa Bucchi,et al.
Wiley
AIMS Nfix is a transcription factor belonging to the Nuclear Factor I (NFI) family comprising four members (Nfia,b,c,x). Nfix plays important roles in the development and function of several organs. In muscle development, Nfix controls the switch from embryonic to fetal myogenesis by promoting fast twitching fibers. In the adult muscle, following injury, lack of Nfix impairs regeneration, inducing higher content of slow-twiching fibers. Nfix is expressed also in the heart but its function has been never investigated before. We studied Nfix role in this organ. METHODS Using Nfix-null and WT mice we analyzed: 1) the expression pattern of Nfix during development by qPCR and 2) the functional alterations caused by its absence, by in vivo telemetry and in vitro patch clamp analysis. RESULTS AND CONCLUSIONS Nfix expression start in the heart from E12.5. Adult hearts of Nfix-null mice show a hearts morphology and sarcomeric proteins expression similar to WT. However, Nfix-null animals show tachycardia that derives form an intrinsic higher beating rate of the sinus node (SAN). Molecular and functional analysis revealed that sinoatrial cells of Nfix-null mice express a significanlty larger L-type calcium current (Cacna1d + Cacna1c). Interestigly, downregulation of Nfix by sh-RNA in primary cultures of neonatal rat ventricular cardiomyoytes induced a similar increase in their spontanous beating rate and in ICaL current. In conclusion, our data provide the first demonstration of a role of Nfix that, increasing the L-type calcium current, modulates heart rate.


Gene- and variant-specific efficacy of serum/glucocorticoid-regulated kinase 1 inhibition in long QT syndrome types 1 and 2
Federica Giannetti, Miriam Barbieri, Assad Shiti, Simona Casini, Philip T Sager, Saumya Das, Sabindra Pradhananga, Dinesh Srinivasan, Saranda Nimani, Nicolò Alerni,et al.
Oxford University Press (OUP)
Abstract Aims Current long QT syndrome (LQTS) therapy, largely based on beta-blockade, does not prevent arrhythmias in all patients; therefore, novel therapies are warranted. Pharmacological inhibition of the serum/glucocorticoid-regulated kinase 1 (SGK1-Inh) has been shown to shorten action potential duration (APD) in LQTS type 3. We aimed to investigate whether SGK1-Inh could similarly shorten APD in LQTS types 1 and 2. Methods and results Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and hiPSC-cardiac cell sheets (CCS) were obtained from LQT1 and LQT2 patients; CMs were isolated from transgenic LQT1, LQT2, and wild-type (WT) rabbits. Serum/glucocorticoid-regulated kinase 1 inhibition effects (300 nM–10 µM) on field potential durations (FPD) were investigated in hiPSC-CMs with multielectrode arrays; optical mapping was performed in LQT2 CCS. Whole-cell and perforated patch clamp recordings were performed in isolated LQT1, LQT2, and WT rabbit CMs to investigate SGK1-Inh (3 µM) effects on APD. In all LQT2 models across different species (hiPSC-CMs, hiPSC-CCS, and rabbit CMs) and independent of the disease-causing variant (KCNH2-p.A561V/p.A614V/p.G628S/IVS9-28A/G), SGK1-Inh dose-dependently shortened FPD/APD at 0.3–10 µM (by 20–32%/25–30%/44–45%). Importantly, in LQT2 rabbit CMs, 3 µM SGK1-Inh normalized APD to its WT value. A significant FPD shortening was observed in KCNQ1-p.R594Q hiPSC-CMs at 1/3/10 µM (by 19/26/35%) and in KCNQ1-p.A341V hiPSC-CMs at 10 µM (by 29%). No SGK1-Inh-induced FPD/APD shortening effect was observed in LQT1 KCNQ1-p.A341V hiPSC-CMs or KCNQ1-p.Y315S rabbit CMs at 0.3–3 µM. Conclusion A robust SGK1-Inh-induced APD shortening was observed across different LQT2 models, species, and genetic variants but less consistently in LQT1 models. This suggests a genotype- and variant-specific beneficial effect of this novel therapeutic approach in LQTS.


PITX2 gain-of-function mutation associated with atrial fibrillation alters mitochondrial activity in human iPSC atrial-like cardiomyocytes
Patrizia Benzoni, Lorenzo Da Dalt, Noemi Elia, Vera Popolizio, Alessandro Cospito, Federica Giannetti, Patrizia Dell’Era, Morten S. Olesen, Annalisa Bucchi, Mirko Baruscotti,et al.
Frontiers Media SA
Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide; however, the underlying causes of AF initiation are still poorly understood, particularly because currently available models do not allow in distinguishing the initial causes from maladaptive remodeling that induces and perpetuates AF. Lately, the genetic background has been proven to be important in the AF onset. iPSC-derived cardiomyocytes, being patient- and mutation-specific, may help solve this diatribe by showing the initial cell-autonomous changes underlying the development of the disease. Transcription factor paired-like homeodomain 2 (PITX2) has been identified as a key regulator of atrial development/differentiation, and the PITX2 genomic locus has the highest association with paroxysmal AF. PITX2 influences mitochondrial activity, and alterations in either its expression or function have been widely associated with AF. In this work, we investigate the activity of mitochondria in iPSC-derived atrial cardiomyocytes (aCMs) obtained from a young patient (24 years old) with paroxysmal AF, carrying a gain-of-function mutation in PITX2 (rs138163892) and from its isogenic control (CTRL) in which the heterozygous point mutation has been reverted to WT. PITX2 aCMs show a higher mitochondrial content, increased mitochondrial activity, and superoxide production under basal conditions when compared to CTRL aCMs. However, increasing mitochondrial workload by FCCP or β-adrenergic stimulation allows us to unmask mitochondrial defects in PITX2 aCMs, which are incapable of responding efficiently to the higher energy demand, determining ATP deficiency.


Use of hiPSC-Derived Cardiomyocytes to Rule Out Proarrhythmic Effects of Drugs: The Case of Hydroxychloroquine in COVID-19
Luca Sala, Vladislav Leonov, Manuela Mura, Federica Giannetti, Aleksandr Khudiakov, Alessandra Moretti, Lia Crotti, Massimiliano Gnecchi, and Peter J. Schwartz
Frontiers Media SA
In the early phases of the COVID-19 pandemic, drug repurposing was widely used to identify compounds that could improve the prognosis of symptomatic patients infected by SARS-CoV-2. Hydroxychloroquine (HCQ) was one of the first drugs used to treat COVID-19 due to its supposed capacity of inhibiting SARS-CoV-2 infection and replication in vitro. While its efficacy is debated, HCQ has been associated with QT interval prolongation and potentially Torsades de Pointes, especially in patients predisposed to developing drug-induced Long QT Syndrome (LQTS) as silent carriers of variants associated with congenital LQTS. If confirmed, these effects represent a limitation to the at-home use of HCQ for COVID-19 infection as adequate ECG monitoring is challenging. We investigated the proarrhythmic profile of HCQ with Multi-Electrode Arrays after exposure of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from two healthy donors, one asymptomatic and two symptomatic LQTS patients. We demonstrated that: I) HCQ induced a concentration-dependent Field Potential Duration (FPD) prolongation and halted the beating at high concentration due to the combined effect of HCQ on multiple ion currents. II) hiPSC-CMs from healthy or asymptomatic carriers tolerated higher concentrations of HCQ and showed lower susceptibility to HCQ-induced electrical abnormalities regardless of baseline FPD. These findings agree with the clinical safety records of HCQ and demonstrated that hiPSC-CMs potentially discriminates symptomatic vs. asymptomatic mutation carriers through pharmacological interventions. Disease-specific cohorts of hiPSC-CMs may be a valid preliminary addition to assess drug safety in vulnerable populations, offering rapid preclinical results with valuable translational relevance for precision medicine.


The funny current: Even funnier than 40 years ago. Uncanonical expression and roles of HCN/f channels all over the body
Patrizia Benzoni, Giorgia Bertoli, Federica Giannetti, Chiara Piantoni, Raffaella Milanesi, Matteo Pecchiari, Andrea Barbuti, Mirko Baruscotti, and Annalisa Bucchi
Elsevier BV



PCSK9 deficiency rewires heart metabolism and drives heart failure with preserved ejection fraction
Lorenzo Da Dalt, Laura Castiglioni, Andrea Baragetti, Matteo Audano, Monika Svecla, Fabrizia Bonacina, Silvia Pedretti, Patrizia Uboldi, Patrizia Benzoni, Federica Giannetti,et al.
Oxford University Press (OUP)
Abstract Aims PCSK9 is secreted into the circulation, mainly by the liver, and interacts with low-density lipoprotein receptor (LDLR) homologous and non-homologous receptors, including CD36, thus favouring their intracellular degradation. As PCSK9 deficiency increases the expression of lipids and lipoprotein receptors, thus contributing to cellular lipid accumulation, we investigated whether this could affect heart metabolism and function. Methods and results Wild-type (WT), Pcsk9 KO, Liver conditional Pcsk9 KO and Pcsk9/Ldlr double KO male mice were fed for 20 weeks with a standard fat diet and then exercise resistance, muscle strength, and heart characteristics were evaluated. Pcsk9 KO presented reduced running resistance coupled to echocardiographic abnormalities suggestive of heart failure with preserved ejection fraction (HFpEF). Heart mitochondrial activity, following maximal coupled and uncoupled respiration, was reduced in Pcsk9 KO mice compared to WT mice and was coupled to major changes in cardiac metabolism together with increased expression of LDLR and CD36 and with lipid accumulation. A similar phenotype was observed in Pcsk9/Ldlr DKO, thus excluding a contribution for LDLR to cardiac impairment observed in Pcsk9 KO mice. Heart function profiling of the liver selective Pcsk9 KO model further excluded the involvement of circulating PCSK9 in the development of HFpEF, pointing to a possible role locally produced PCSK9. Concordantly, carriers of the R46L loss-of-function variant for PCSK9 presented increased left ventricular mass but similar ejection fraction compared to matched control subjects. Conclusion PCSK9 deficiency impacts cardiac lipid metabolism in an LDLR independent manner and contributes to the development of HFpEF.


Dual role of miR-1 in the development and function of sinoatrial cells
P. Benzoni, L. Nava, F. Giannetti, G. Guerini, A. Gualdoni, C. Bazzini, R. Milanesi, A. Bucchi, M. Baruscotti, and A. Barbuti
Elsevier BV



A detailed characterization of the hyperpolarization-activated “funny” current (I <inf>f</inf>) in human-induced pluripotent stem cell (iPSC)–derived cardiomyocytes with pacemaker activity
Federica Giannetti, Patrizia Benzoni, Giulia Campostrini, Raffaella Milanesi, Annalisa Bucchi, Mirko Baruscotti, Patrizia Dell’Era, Alessandra Rossini, and Andrea Barbuti
Springer Science and Business Media LLC
AbstractProperties of the funny current (If) have been studied in several animal and cellular models, but so far little is known concerning its properties in human pacemaker cells. This work provides a detailed characterization of If in human-induced pluripotent stem cell (iPSC)–derived pacemaker cardiomyocytes (pCMs), at different time points. Patch-clamp analysis showed that If density did not change during differentiation; however, after day 30, it activates at more negative potential and with slower time constants. These changes are accompanied by a slowing in beating rate. If displayed the voltage-dependent block by caesium and reversed (Erev) at − 22 mV, compatibly with the 3:1 K+/Na+ permeability ratio. Lowering [Na+]o (30 mM) shifted the Erev to − 39 mV without affecting conductance. Increasing [K+]o (30 mM) shifted the Erev to − 15 mV with a fourfold increase in conductance. pCMs express mainly HCN4 and HCN1 together with the accessory subunits CAV3, KCR1, MiRP1, and SAP97 that contribute to the context-dependence of If. Autonomic agonists modulated the diastolic depolarization, and thus rate, of pCMs. The adrenergic agonist isoproterenol induced rate acceleration and a positive shift of If voltage-dependence (EC50 73.4 nM). The muscarinic agonists had opposite effects (Carbachol EC50, 11,6 nM). Carbachol effect was however small but it could be increased by pre-stimulation with isoproterenol, indicating low cAMP levels in pCMs. In conclusion, we demonstrated that pCMs display an If with the physiological properties expected by pacemaker cells and may thus represent a suitable model for studying human If-related sinus arrhythmias.


Generation of the induced human pluripotent stem cell lines CSSi009-A from a patient with a GNB5 pathogenic variant, and CSSi010-A from a CRISPR/Cas9 engineered GNB5 knock-out human cell line
Natascia Malerba, Patrizia Benzoni, Gabriella Maria Squeo, Raffaella Milanesi, Federica Giannetti, Lynette G. Sadleir, Gemma Poke, Bartolomeo Augello, Anna Irma Croce, Andrea Barbuti,et al.
Elsevier BV

RECENT SCHOLAR PUBLICATIONS

Rescue of loss‐of‐function long QT syndrome‐associated mutations in K_V7.1/KCNE1 by the endocannabinoid N‐arachidonoyl‐L‐serine (ARA‐S)
I Hiniesto‐Iigo, A Sridhar, J Louradour, A Cruz, S Lundholm, ...
British Journal of Pharmacology 2025



Genetic variants risk assessment for Long QT Syndrome through machine learning and multielectrode array recordings
A Khudiakov, M Mura, F Giannetti, V Leonov, C Alberio, M Eskandr, ...
medRxiv, 2025.03. 25.25324187 2025



Therapeutic efficacy of mexiletine for long QT syndrome type 2: evidence from human induced pluripotent stem cell–derived cardiomyocytes, transgenic rabbits, and patients
L Crotti, R Neves, F Dagradi, G Musu, F Giannetti, JM Bos, M Barbieri, ...
Circulation 150 (7), 531-543 2024



Striatin knock out induces a gain of function of I_Na and impaired Ca²⁺ handling in mESC‐derived cardiomyocytes
P Benzoni, M Arici, F Giannetti, A Cospito, R Prevostini, C Volani, ...
Acta Physiologica 240 (8), e14160 2024



A gain of function mutation in PITX2c gene linked to atrial fibrillation alters mitochondrial function and membrane excitability
P Benzoni, L Da Dalt, A Cospito, V Popolizio, F Giannetti, C Ruberti, ...
Vascular pharmacology 155, 107298 2024



Use of hiPSC-derived cardiomyocytes to study LQTS-variant specific proarrhythmic effects of drugs
L Sala, A Khudiakov, M Mura, V Leonov, F Giannetti, L Crotti, M Gnecchi, ...
Vascular pharmacology 155, 107347 2024



CE-482905-003 EFFICACY OF MEXILETINE FOR LQT2: EVIDENCE FROM HIPSC-DERIVED CARDIOMYOCYTES, TRANSGENIC RABBITS AND PATIENTS
L Crotti, RA Neves, F Dagradi, G Musu, F Giannetti, JM Bos, M Barbieri, ...
Heart Rhythm 21 (5), S33 2024



PITX2 gain-of-function mutation associated with atrial fibrillation alters mitochondrial activity in human iPSC atrial-like cardiomyocytes
P Benzoni, L Da Dalt, N Elia, V Popolizio, A Cospito, F Giannetti, ...
Frontiers in Physiology 14, 1250951 2023



Lack of the transcription factor Nfix causes tachycardia in mice sinus node and rats neonatal cardiomyocytes
S Landi, F Giannetti, P Benzoni, G Campostrini, G Rossi, C Piantoni, ...
Acta Physiologica 239 (2), e13981 2023



Gene-and variant-specific efficacy of serum/glucocorticoid-regulated kinase 1 inhibition in long QT syndrome types 1 and 2
F Giannetti, M Barbieri, A Shiti, S Casini, PT Sager, S Das, ...
Europace 25 (5), euad094 2023



PCSK9 modulates cardiac metabolism and impacts HFpEF
L Da Dalt, L Castiglioni, A Baragetti, M Audano, M Svecla, F Bonacina, ...
Atherosclerosis 355, 1 2022



HIPS AND MES AS A CELLULAR MODEL TO STUDY THE MECHANISMS BEHIND ARRHYTHMIAS.
F Giannetti
Universit degli Studi di Milano 2022



Use of hiPSC-derived cardiomyocytes to rule out proarrhythmic effects of drugs: the case of hydroxychloroquine in COVID-19
L Sala, V Leonov, M Mura, F Giannetti, A Khudiakov, A Moretti, L Crotti, ...
Frontiers in Physiology 12, 730127 2022



The funny current: Even funnier than 40 years ago. Uncanonical expression and roles of HCN/f channels all over the body
P Benzoni, G Bertoli, F Giannetti, C Piantoni, R Milanesi, M Pecchiari, ...
Progress in biophysics and molecular biology 166, 189-204 2021



PCSK9 deficiency rewires heart metabolism and drives heart failure with preserved ejection fraction
L Da Dalt, L Castiglioni, A Baragetti, M Audano, M Svecla, F Bonacina, ...
European Heart Journal 42 (32), 3078-3090 2021



Hyperglycemic condition mimics tgrls lipid accumulation in cardiomyocytes derived from human-IPSCS
L Da Dalt, F Giannetti, P Benzoni, M Audano, A Barbuti, N Mitro, ...
Atherosclerosis 331, e124 2021



Dual role of miR-1 in the development and function of sinoatrial cells
P Benzoni, L Nava, F Giannetti, G Guerini, A Gualdoni, C Bazzini, ...
Journal of Molecular and Cellular Cardiology 157, 104-112 2021



A detailed characterization of the hyperpolarization-activated “funny” current (I_f) in human-induced pluripotent stem cell (iPSC)–derived cardiomyocytes with
F Giannetti, P Benzoni, G Campostrini, R Milanesi, A Bucchi, M Baruscotti, ...
Pflgers Archiv-European Journal of Physiology 473 (7), 1009-1021 2021



When multiple caveolins make the difference: Cav1 partly compensates Cav3 alterations and rescues ion channels expression
P Benzoni, F Giannetti, A Cospito, A Rossini, A Bucchi, M Baruscotti, ...
EP Europace 23 (Supplement_3), euab116. 535 2021



Impact of PCSK9 on human-IPSC derived cardiomyocyte mitochondrial function and metabolism
L Da Dalt, F Giannetti, P Benzoni, M Audano, A Barbuti, N Mitro, ...
Atherosclerosis 315, e86 2020

MOST CITED SCHOLAR PUBLICATIONS

PCSK9 deficiency rewires heart metabolism and drives heart failure with preserved ejection fraction
L Da Dalt, L Castiglioni, A Baragetti, M Audano, M Svecla, F Bonacina, ...
European Heart Journal 42 (32), 3078-3090 2021
Citations: 93



A detailed characterization of the hyperpolarization-activated “funny” current (I_f) in human-induced pluripotent stem cell (iPSC)–derived cardiomyocytes with
F Giannetti, P Benzoni, G Campostrini, R Milanesi, A Bucchi, M Baruscotti, ...
Pflgers Archiv-European Journal of Physiology 473 (7), 1009-1021 2021
Citations: 31



The funny current: Even funnier than 40 years ago. Uncanonical expression and roles of HCN/f channels all over the body
P Benzoni, G Bertoli, F Giannetti, C Piantoni, R Milanesi, M Pecchiari, ...
Progress in biophysics and molecular biology 166, 189-204 2021
Citations: 22



Gene-and variant-specific efficacy of serum/glucocorticoid-regulated kinase 1 inhibition in long QT syndrome types 1 and 2
F Giannetti, M Barbieri, A Shiti, S Casini, PT Sager, S Das, ...
Europace 25 (5), euad094 2023
Citations: 12



Use of hiPSC-derived cardiomyocytes to rule out proarrhythmic effects of drugs: the case of hydroxychloroquine in COVID-19
L Sala, V Leonov, M Mura, F Giannetti, A Khudiakov, A Moretti, L Crotti, ...
Frontiers in Physiology 12, 730127 2022
Citations: 10



Dual role of miR-1 in the development and function of sinoatrial cells
P Benzoni, L Nava, F Giannetti, G Guerini, A Gualdoni, C Bazzini, ...
Journal of Molecular and Cellular Cardiology 157, 104-112 2021
Citations: 10



Therapeutic efficacy of mexiletine for long QT syndrome type 2: evidence from human induced pluripotent stem cell–derived cardiomyocytes, transgenic rabbits, and patients
L Crotti, R Neves, F Dagradi, G Musu, F Giannetti, JM Bos, M Barbieri, ...
Circulation 150 (7), 531-543 2024
Citations: 8



Striatin knock out induces a gain of function of I_Na and impaired Ca²⁺ handling in mESC‐derived cardiomyocytes
P Benzoni, M Arici, F Giannetti, A Cospito, R Prevostini, C Volani, ...
Acta Physiologica 240 (8), e14160 2024
Citations: 4



Lack of the transcription factor Nfix causes tachycardia in mice sinus node and rats neonatal cardiomyocytes
S Landi, F Giannetti, P Benzoni, G Campostrini, G Rossi, C Piantoni, ...
Acta Physiologica 239 (2), e13981 2023
Citations: 4



PITX2 gain-of-function mutation associated with atrial fibrillation alters mitochondrial activity in human iPSC atrial-like cardiomyocytes
P Benzoni, L Da Dalt, N Elia, V Popolizio, A Cospito, F Giannetti, ...
Frontiers in Physiology 14, 1250951 2023
Citations: 2



Generation of the induced human pluripotent stem cell lines CSSi009-A from a patient with a GNB5 pathogenic variant, and CSSi010-A from a CRISPR/Cas9 engineered GNB5 knock-out
N Malerba, P Benzoni, GM Squeo, R Milanesi, F Giannetti, LG Sadleir, ...
Stem Cell Research 40, 101547 2019
Citations: 2



Hypocalcemia and the QT segment (presentation of 2 personal cases)
T Dellocchio, R Florio, F Giannetti, A Manetti, R Vergassola
Cardiologia Pratica 25 (3), 253-259 1974
Citations: 1