Rescue of loss-of-function long QT syndrome-associated mutations in KV7.1/KCNE1 by the endocannabinoid N-arachidonoyl-L-serine (ARA-S) Irene Hiniesto‐Iñigo, Akshay Sridhar, Julien Louradour, Alicia De la Cruz, Siri Lundholm, et al. British Journal of Pharmacology, 2025 Background 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, et al. Circulation, 2024 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 <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 INa and impaired Ca2+ handling in mESC-derived cardiomyocytes P. Benzoni, M. Arici, F. Giannetti, A. Cospito, R. Prevostini, et al. Acta Physiologica, 2024 AimStriatin (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.
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, et al. Acta Physiologica, 2023 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, et al. Europace, 2023 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, et al. Frontiers in Physiology, 2023 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, et al. Frontiers in Physiology, 2022 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.
PCSK9 deficiency rewires heart metabolism and drives heart failure with preserved ejection fraction Lorenzo Da Dalt, Laura Castiglioni, Andrea Baragetti, Matteo Audano, Monika Svecla, et al. European Heart Journal, 2021 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.
Machine learning-guided risk stratification for Long QT Syndrome genetic variants with hiPSC-derived cardiomyocytes A Khudiakov, M Mura, F Giannetti, V Leonov, C Alberio, M Eskandr, ... Cardiovascular Research, cvag105 , 2026 2026
SGK1-inhibition restores cardiac repolarization in LQT2 rabbits and LQT3 mice by reducing late sodium current M Barbieri, S Casini, J Louradour, TM de Waal, N Alerni, AO Verkerk, ... Pharmacological Research, 108189 , 2026 2026
Rescue of loss‐of‐function long QT syndrome‐associated mutations in K V 7.1/KCNE1 by the endocannabinoid N‐arachidonoyl‐L‐serine (ARA‐S) I Hiniesto‐Iñigo, A Sridhar, J Louradour, A De la Cruz, S Lundholm, ... British Journal of Pharmacology 182 (13), 2861-2877 , 2025 2025 Citations: 4
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 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 2024 Citations: 34
Striatin knock out induces a gain of function of I Na and impaired Ca 2+ handling in mESC‐derived cardiomyocytes P Benzoni, M Arici, F Giannetti, A Cospito, R Prevostini, C Volani, ... Acta Physiologica 240 (8), e14160 , 2024 2024 Citations: 6
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 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 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 (June 2024), 107347-107347 , 2024 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 2023 Citations: 9
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 2023 Citations: 7
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 2023 Citations: 22
PCSK9 modulates cardiac metabolism and impacts HFpEF L Da Dalt, L Castiglioni, A Baragetti, M Audano, M Svecla, F Bonacina, ... Atherosclerosis 355, 1 , 2022 2022
HIPS AND MES AS A CELLULAR MODEL TO STUDY THE MECHANISMS BEHIND ARRHYTHMIAS. F Giannetti Università degli Studi di Milano , 2022 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 2022 Citations: 13
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 2021 Citations: 26
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 2021 Citations: 121
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 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 2021 Citations: 17
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, ... Pflügers Archiv-European Journal of Physiology 473 (7), 1009-1021 , 2021 2021 Citations: 41
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 2021 Citations: 121
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, ... Pflügers Archiv-European Journal of Physiology 473 (7), 1009-1021 , 2021 2021 Citations: 41
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 2024 Citations: 34
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 2021 Citations: 26
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 2023 Citations: 22
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 2021 Citations: 17
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 2022 Citations: 13
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 2023 Citations: 9
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 2023 Citations: 7
Striatin knock out induces a gain of function of I Na and impaired Ca 2+ handling in mESC‐derived cardiomyocytes P Benzoni, M Arici, F Giannetti, A Cospito, R Prevostini, C Volani, ... Acta Physiologica 240 (8), e14160 , 2024 2024 Citations: 6
Rescue of loss‐of‐function long QT syndrome‐associated mutations in K V 7.1/KCNE1 by the endocannabinoid N‐arachidonoyl‐L‐serine (ARA‐S) I Hiniesto‐Iñigo, A Sridhar, J Louradour, A De la Cruz, S Lundholm, ... British Journal of Pharmacology 182 (13), 2861-2877 , 2025 2025 Citations: 4
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 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 1974 Citations: 1
Machine learning-guided risk stratification for Long QT Syndrome genetic variants with hiPSC-derived cardiomyocytes A Khudiakov, M Mura, F Giannetti, V Leonov, C Alberio, M Eskandr, ... Cardiovascular Research, cvag105 , 2026 2026
SGK1-inhibition restores cardiac repolarization in LQT2 rabbits and LQT3 mice by reducing late sodium current M Barbieri, S Casini, J Louradour, TM de Waal, N Alerni, AO Verkerk, ... Pharmacological Research, 108189 , 2026 2026
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 2025
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 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 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 (June 2024), 107347-107347 , 2024 2024
PCSK9 modulates cardiac metabolism and impacts HFpEF L Da Dalt, L Castiglioni, A Baragetti, M Audano, M Svecla, F Bonacina, ... Atherosclerosis 355, 1 , 2022 2022
