المؤلفون: Juan R. Gimeno, Iacopo Olivotto, Ana Isabel Rodríguez, Carolyn Y. Ho, Adrián Fernández, Alejandro Quiroga, Mari Angeles Espinosa, Cristina Gómez‐González, María Robledo, Lucas Tojal‐Sierra, Sharlene M. Day, Anjali Owens, Roberto Barriales‐Villa, Jose María Larrañaga, Jose Rodríguez‐Palomares, Maribel González‐del‐Hoyo, Jesús Piqueras‐Flores, Nosheen Reza, Olga Chumakova, Euan A. Ashley, Victoria Parikh, Matthew Wheeler, Daniel Jacoby, Alexandre C. Pereira, Sara Saberi, Adam S. Helms, Eduardo Villacorta, María Gallego‐Delgado, Daniel deCastro, Fernando Domínguez, Tomás Ripoll‐Vera, Esther Zorio‐Grima, José Carlos Sánchez‐Martínez, Ana García‐Álvarez, Elena Arbelo, María Victoria Mogollón, María Eugenia Fuentes‐Cañamero, Elias Grande, Carlos Peña, Lorenzo Monserrat, Neal K. Lakdawala, Dilema International Cardiomyopathy and Heart Failure Registry and international SHaRe (Sarcomeric Human Cardiomyopathy Registry) Investigators group

المصدر: ESC Heart Failure, Vol 9, Iss 4, Pp 2189-2198 (2022)

مصطلحات موضوعية: Hypertrophic cardiomyopathy, COVID‐19, SARS‐CoV‐2 infection, Heart failure, Registry, Prognosis, Diseases of the circulatory (Cardiovascular) system, RC666-701

الوصف: Abstract Aims To describe the natural history of SARS‐CoV‐2 infection in patients with hypertrophic cardiomyopathy (HCM) compared with a control group and to identify predictors of adverse events. Methods and results Three hundred and five patients [age 56.6 ± 16.9 years old, 191 (62.6%) male patients] with HCM and SARS‐Cov‐2 infection were enrolled. The control group consisted of 91 131 infected individuals. Endpoints were (i) SARS‐CoV‐2 related mortality and (ii) severe clinical course [death or intensive care unit (ICU) admission]. New onset of atrial fibrillation, ventricular arrhythmias, shock, stroke, and cardiac arrest were also recorded. Sixty‐nine (22.9%) HCM patients were hospitalized for non‐ICU level care, and 21 (7.0%) required ICU care. Seventeen (5.6%) died: eight (2.6%) of respiratory failure, four (1.3%) of heart failure, two (0.7%) suddenly, and three (1.0%) due to other SARS‐CoV‐2‐related complications. Covariates associated with mortality in the multivariable were age {odds ratio (OR) per 10 year increase 2.25 [95% confidence interval (CI): 1.12–4.51], P = 0.0229}, baseline New York Heart Association class [OR per one‐unit increase 4.01 (95%CI: 1.75–9.20), P = 0.0011], presence of left ventricular outflow tract obstruction [OR 5.59 (95%CI: 1.16–26.92), P = 0.0317], and left ventricular systolic impairment [OR 7.72 (95%CI: 1.20–49.79), P = 0.0316]. Controlling for age and sex and comparing HCM patients with a community‐based SARS‐CoV‐2 cohort, the presence of HCM was associated with a borderline significant increased risk of mortality OR 1.70 (95%CI: 0.98–2.91, P = 0.0600). Conclusions Over one‐fourth of HCM patients infected with SARS‐Cov‐2 required hospitalization, including 6% in an ICU setting. Age and cardiac features related to HCM, including baseline functional class, left ventricular outflow tract obstruction, and systolic impairment, conveyed increased risk of mortality.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2055-5822Test

الوصول الحر: https://doaj.org/article/91483f6a810740f68b374d86c8670633Test

المؤلفون: Lara Milián, Pilar Molina, María Oliver-Ferrándiz, Carlos Fernández-Sellers, Ana Monzó, Rafael Sánchez-Sánchez, Aitana Braza-Boils, Manuel Mata, Esther Zorio

المصدر: International Journal of Molecular Sciences, Vol 24, Iss 21, p 15696 (2023)

مصطلحات موضوعية: adipose-derived stem cells, mesenchymal cell, cartilage regeneration, bone regeneration, tissue engineering, in vitro disease models, Biology (General), QH301-705.5, Chemistry, QD1-999

الوصف: Advances in regenerative medicine have enabled the search for new solutions to current health problems in so far unexplored fields. Thus, we focused on cadaveric subcutaneous fat as a promising source of adipose-derived stem cells (ADSCs) that have potential to differentiate into different cell lines. With this aim, we isolated and characterized ADSCs from cadaveric samples with a postmortem interval ranging from 30 to 55 h and evaluated their ability to differentiate into chondrocytes or osteocytes. A commercial ADSC line was used as reference. Morphological and protein expression analyses were used to confirm the final stage of differentiation. Eight out of fourteen samples from patients were suitable to complete the whole protocol. Cadaveric ADSCs exhibited features of stem cells based upon several markers: CD29 (84.49 ± 14.07%), CD105 (94.38 ± 2.09%), and CD44 (99.77 ± 0.32%). The multiparametric assessment of differentiation confirmed the generation of stable lines of chondrocytes and osteocytes. In conclusion, we provide evidence supporting the feasibility of obtaining viable postmortem human subcutaneous fat ADSCs with potential application in tissue engineering and research fields.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/1422-0067/24/21/15696Test; https://doaj.org/toc/1661-6596Test; https://doaj.org/toc/1422-0067Test

الوصول الحر: https://doaj.org/article/c95f6faca51449c8a5493fe9105f98cdTest

المؤلفون: Julia Martínez-Solé, María Sabater-Molina, Aitana Braza-Boïls, Juan J. Santos-Mateo, Pilar Molina, Luis Martínez-Dolz, Juan R. Gimeno, Esther Zorio

المصدر: Frontiers in Cardiovascular Medicine, Vol 8 (2022)

مصطلحات موضوعية: sports, exercise, arrhythmogenic cardiomyopathy, disease progression, risk factors, Diseases of the circulatory (Cardiovascular) system, RC666-701

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fcvm.2021.816280/fullTest; https://doaj.org/toc/2297-055XTest

الوصول الحر: https://doaj.org/article/db24235ca41d46bb98190f62c0a3ef88Test

المؤلفون: Maria Sabater Molina, Elisa Nicolás Rocamora, Asunción Iborra Bendicho, Elisa García Vázquez, Esther Zorio, Fernando Domínguez Rodriguez, Cristina Gil Ortuño, Ana Isabel Rodríguez, Antonio J Sánchez-López, Rubén Jara Rubio, Antonio Moreno-Docón, Pedro J Marcos, Pablo García Pavía, Roberto Barriales Villa, Juan R Gimeno Blanes

المصدر: PLoS ONE, Vol 17, Iss 2, p e0263140 (2022)

مصطلحات موضوعية: Medicine, Science

الوصف: BackgroundInfection by the SARS-Cov-2 virus produces in humans a disease of highly variable and unpredictable severity. The presence of frequent genetic single nucleotide polymorphisms (SNPs) in the population might lead to a greater susceptibility to infection or an exaggerated inflammatory response. SARS-CoV-2 requires the presence of the ACE2 protein to enter in the cell and ACE2 is a regulator of the renin-angiotensin system. Accordingly, we studied the associations between 8 SNPs from AGTR1, ACE2 and ACE genes and the severity of the disease produced by the SARS-Cov-2 virus.Methods318 (aged 59.6±17.3 years, males 62.6%) COVID-19 patients were grouped based on the severity of symptoms: Outpatients (n = 104, 32.7%), hospitalized on the wards (n = 73, 23.0%), Intensive Care Unit (ICU) (n = 84, 26.4%) and deceased (n = 57, 17.9%). Comorbidity data (diabetes, hypertension, obesity, lung disease and cancer) were collected for adjustment. Genotype distribution of 8 selected SNPs among the severity groups was analyzed.ResultsFour SNPs in ACE2 were associated with the severity of disease. While rs2074192 andrs1978124showed a protector effectassuming an overdominant model of inheritance (G/A vs. GG-AA, OR = 0.32, 95%CI = 0.12-0.82; p = 0.016 and A/G vs. AA-GG, OR = 0.37, 95%CI: 0.14-0.96; p = 0.038, respectively); the SNPs rs2106809 and rs2285666were associated with an increased risk of being hospitalized and a severity course of the disease with recessive models of inheritance (C/C vs. T/C-T/T, OR = 11.41, 95% CI: 1.12-115.91; p = 0.012) and (A/A vs. GG-G/A, OR = 12.61, 95% CI: 1.26-125.87; p = 0.0081). As expected, an older age (OR = 1.47), male gender (OR = 1.98) and comorbidities (OR = 2.52) increased the risk of being admitted to ICU or death vs more benign outpatient course. Multivariable analysis demonstrated the role of the certain genotypes (ACE2) with the severity of COVID-19 (OR: 0.31, OR 0.37 for rs2074192 and rs1978124, and OR = 2.67, OR = 2.70 for rs2106809 and rs2285666, respectively). Hardy-Weinberg equilibrium in hospitalized group for I/D SNP in ACE was not showed (pConclusionsDifferent genetic variants in ACE2 were associated with a severe clinical course and death groups of patients with COVID-19. ACE2 common SNPs in the population might modulate severity of COVID-19 infection independently of other known markers like gender, age and comorbidities.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1932-6203Test

الوصول الحر: https://doaj.org/article/c2363fd06a5b4672831a8938afe0b115Test

المؤلفون: Edgardo Alania-Torres, Herminio Morillas-Climent, Alexandre García-Escrivá, Paul Vinueza-Buitrón, Inmaculada Poquet-Catalá, Esther Zorio, Ignacio José Sánchez-Lázaro, Emilio Galcerá-Jornet, Alfonso Valle-Muñoz

المصدر: Frontiers in Cardiovascular Medicine, Vol 8 (2021)

مصطلحات موضوعية: myocarditis, vaccine, COVID-19, arrhythmogenic left ventricular cardiomyopathy, myopathy, Diseases of the circulatory (Cardiovascular) system, RC666-701

الوصف: Arrhythmogenic left ventricular cardiomyopathy (ALVC) is a rare heritable heart-muscle disorder characterized by a progressive loss of left ventricular myocardium and its replacement by fibrofatty tissue. Myocarditis is an inflammatory disease of the heart that may occur secondary to infections, immune system activation or exposure to drugs. Hot phases of ALVC present with chest pain and troponin rise, mimicking acute viral myocarditis and indicate a progression of the disease. Recently, myocarditis has also been described as an infrequent complication of coronavirus disease 2019 (Covid-19) mRNA vaccines. We herein report for the first time a case of probable myocarditis induced by Covid-19 vaccine in a patient with previous medical history of ALVC. We aim to highlight the common characteristics of ALVC and Covid-19 vaccine myocarditis and work through the differential diagnosis of these two entities.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fcvm.2021.759119/fullTest; https://doaj.org/toc/2297-055XTest

الوصول الحر: https://doaj.org/article/60ab4216056c442dadba0ce44bffb426Test

المؤلفون: Julia Martínez-Solé, María Sabater-Molina, Aitana Braza-Boïls, Juan J. Santos-Mateo, Pilar Molina, Luis Martínez-Dolz, Juan R. Gimeno, Esther Zorio

المصدر: Frontiers in Cardiovascular Medicine, Vol 8 (2021)

مصطلحات موضوعية: sports, exercise, arrhythmogenic cardiomyopathy, disease progression, risk factors, Diseases of the circulatory (Cardiovascular) system, RC666-701

الوصف: Arrhythmogenic cardiomyopathy (ACM) is a genetic cardiac condition characterized by fibrofatty myocardial replacement, either at the right ventricle, at the left ventricle, or with biventricular involvement. Ventricular arrhythmias and heart failure represent its main clinical features. Exercise benefits on mental and physical health are worldwide recognized. However, patients with ACM appear to be an exception. A thorough review of the literature was performed in PubMed searching for original papers with the terms “ARVC AND sports/exercise” and “sudden cardiac death AND sports/exercise.” Additional papers were then identified through other sources and incorporated to the list. All of them had to be based on animal models or clinical series. Information was structured in a regular format, although some data were not available in some papers. A total of 34 papers were selected and processed regarding sports-related sudden cardiac death, pre-clinical models of ACM and sport, and clinical series of ACM patients engaged in sports activities. Eligible papers were identified to obtain pooled data in order to build representative figures showing the global incidence of the most important causes of sudden cardiac death in sports and the global estimates of life-threatening arrhythmic events in ACM patients engaged in sports. Tables and figures illustrate their major characteristics. The scarce points of controversy were discussed in the text. Fundamental concepts were summarized in three main issues: sports may accelerate ACM phenotype with either structural and/or arrhythmic features, restriction may soften the progression, and these rules also apply to phenotype-negative mutation carriers. Additionally, remaining gaps in the current knowledge were also highlighted, namely, the applicability of those fundamental concepts to non-classical ACM phenotypes since left dominant ACM or non-plakophillin-2 genotypes were absent or very poorly represented in the available studies. Hopefully, future research endeavors will provide solid evidence about the safest exercise dose for each patient from a personalized medicine perspective, taking into account a big batch of genetic, epigenetic, and epidemiological variables, for instance, in order to assist clinicians to provide a final tailored recommendation.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fcvm.2021.702560/fullTest; https://doaj.org/toc/2297-055XTest

الوصول الحر: https://doaj.org/article/abd1b23ca2054750a4a9d0402e59c177Test

المؤلفون: Marina Piquer-Gil, Sofía Domenech-Dauder, Marta Sepúlveda-Gómez, Carla Machí-Camacho, Aitana Braza-Boïls, Esther Zorio

المصدر: Biomedicines, Vol 10, Iss 10, p 2619 (2022)

مصطلحات موضوعية: arrhythmogenic cardiomyopathy, ncRNA, lncRNA, miRNA, circRNA, pseudogene, Biology (General), QH301-705.5

الوصف: Arrhythmogenic cardiomyopathy (ACM) is an inherited cardiomyopathy histologically characterized by the replacement of myocardium by fibrofatty infiltration, cardiomyocyte loss, and inflammation. ACM has been defined as a desmosomal disease because most of the mutations causing the disease are located in genes encoding desmosomal proteins. Interestingly, the instable structures of these intercellular junctions in this disease are closely related to a perturbed Wnt/β-catenin pathway. Imbalance in the Wnt/β-catenin signaling and also in the crosslinked Hippo pathway leads to the transcription of proadipogenic and profibrotic genes. Aiming to shed light on the mechanisms by which Wnt/β-catenin and Hippo pathways modulate the progression of the pathological ACM phenotype, the study of non-coding RNAs (ncRNAs) has emerged as a potential source of actionable targets. ncRNAs comprise a wide range of RNA species (short, large, linear, circular) which are able to finely tune gene expression and determine the final phenotype. Some share recognition sites, thus referred to as competing endogenous RNAs (ceRNAs), and ensure a coordinating action. Recent cancer research studies regarding the key role of ceRNAs in Wnt/β-catenin and Hippo pathways modulation pave the way to better understanding the molecular mechanisms underlying ACM.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2227-9059/10/10/2619Test; https://doaj.org/toc/2227-9059Test

الوصول الحر: https://doaj.org/article/866af4ec516a42419025fe00074db6bdTest

المؤلفون: Pilar Molina, Jorge Sanz-Sánchez, Manuel Fenollosa, Marina Martínez-Matilla, Juan Giner, Esther Zorio

المصدر: Forensic Sciences Research, Vol 4, Iss 3, Pp 274-279 (2019)

مصطلحات موضوعية: forensic sciences, forensic pathology, ischemic heart disease, arrhythmogenic cardiomyopathy, family study, Criminal law and procedure, K5000-5582, Public aspects of medicine, RA1-1270

الوصف: Ischemic heart disease (IHD) is the leading cause of sudden cardiac death (SCD) and often non-thrombosed severe coronary stenoses with or without myocardial scars are detected. Left dominant arrhythmogenic cardiomyopathy (LDAC) is a life-threating rare disease which has been more thoroughly studied in the last 10 years. The macroscopic study of an SCD victim was conducted and re-evaluated 9 years later. The cardiological work-up in his first-degree relatives initially comprised an electrocardiogram (ECG) and an echocardiogram. When they were re-evaluted 9 years later, a cardiac magnetic resonance, an ECG-monitoring, an exercise testing and a genetic study were performed and the pedigree was extended accordingly. In 2008, an IHD was suspected in the sports-triggered SCD of a 37-year-old man upon the postmortem (75% stenosis of the left main and circumflex coronary arteries; the subepicardial left ventricular fibrofatty infiltration with mild myocardial degeneration was assumed to be a past myocardial infarction). No cardiomyopathy was identified in any of the two proband’s sisters. Nine years thereafter, distant relatives were diagnosed with LDAC due to a pathogenic desmoplakin mutation. The reanalysis of the two sisters showed ventricular arrhythmias in one of them without structural heart involvement and the reviewed postmortem of the proband was reclassified as LDAC based on the fibrofatty infiltration; both were mutation carriers. The completion of the family study on 19 family members yielded one SCD due to LDAC (the proband), three living patients diagnosed with LDAC (two with a defibrillator), one mutation carrier without structural ventricular involvement, and 14 healthy relatives (who were discharged) with a very good co-segregation of the mutation. Although rare, LDAC exists and sometimes its differential diagnosis with IHD has to be faced. Modifying previous postmortem misdiagnoses can help family screening to further prevent SCDs.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2096-1790Test; https://doaj.org/toc/2471-1411Test

الوصول الحر: https://doaj.org/article/d83bf302b92c4791bb5b65cfdf999837Test

المؤلفون: Jordi Cano, Esther Zorio, Andrea Mazzanti, Miguel Ángel Arnau, Beatriz Trenor, Silvia G. Priori, Javier Saiz, Lucia Romero

المصدر: Frontiers in Pharmacology, Vol 11 (2020)

مصطلحات موضوعية: Long QT Syndrome, flecainide, ranolazine, in-silico model, sodium current channelopathy, V411M, Therapeutics. Pharmacology, RM1-950

الوصف: The prolongation of the QT interval represents the main feature of the long QT syndrome (LQTS), a life-threatening genetic disease. The heterozygous SCN5A V411M mutation of the human sodium channel leads to a LQTS type 3 with severe proarrhythmic effects due to an increase in the late component of the sodium current (INaL). The two sodium blockers flecainide and ranolazine are equally recommended by the current 2015 ESC guidelines to treat patients with LQTS type 3 and persistently prolonged QT intervals. However, awareness of pro-arrhythmic effects of flecainide in LQTS type 3 patients arose upon the study of the SCN5A E1784K mutation. Regarding SCN5A V411M individuals, flecainide showed good results albeit in a reduced number of patients and no evidence supporting the use of ranolazine has ever been released. Therefore, we ought to compare the effect of ranolazine and flecainide in a SCN5A V411M model using an in-silico modeling and simulation approach. We collected clinical data of four patients. Then, we fitted four Markovian models of the human sodium current (INa) to experimental and clinical data. Two of them correspond to the wild type and the heterozygous SCN5A V411M scenarios, and the other two mimic the effects of flecainide and ranolazine on INa. Next, we inserted them into three isolated cell action potential (AP) models for endocardial, midmyocardial and epicardial cells and in a one-dimensional tissue model. The SCN5A V411M mutation produced a 15.9% APD90 prolongation in the isolated endocardial cell model, which corresponded to a 14.3% of the QT interval prolongation in a one-dimensional strand model, in keeping with clinical observations. Although with different underlying mechanisms, flecainide and ranolazine partially countered this prolongation at the isolated endocardial model by reducing the APD90 by 8.7 and 4.3%, and the QT interval by 7.2 and 3.2%, respectively. While flecainide specifically targeted the mutation-induced increase in peak INaL, ranolazine reduced it during the entire AP. Our simulations also suggest that ranolazine could prevent early afterdepolarizations triggered by the SCN5A V411M mutation during bradycardia, as flecainide. We conclude that ranolazine could be used to treat SCN5A V411M patients, specifically when flecainide is contraindicated.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fphar.2020.580481/fullTest; https://doaj.org/toc/1663-9812Test

الوصول الحر: https://doaj.org/article/ff65d0b4f8104354aaf734f3cddc1cf8Test

المؤلفون: Oriol Calvete, Pablo Garcia‐Pavia, Fernando Domínguez, Lluc Mosteiro, Lucía Pérez‐Cabornero, Diego Cantalapiedra, Esther Zorio, Teresa Ramón y Cajal, Maria G. Crespo‐Leiro, Álex Teulé, Conxi Lázaro, Manuel M. Morente, Miguel Urioste, Javier Benitez

المصدر: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, Vol 8, Iss 18 (2019)

مصطلحات موضوعية: cardiac angiosarcoma, cell cycle arrest, damage response, POT1, VEGF/angiogenesis pathway, Diseases of the circulatory (Cardiovascular) system, RC666-701

الوصف: Background Mutations in the POT1 gene explain abnormally long telomeres and multiple tumors including cardiac angiosarcomas (CAS). However, the link between long telomeres and tumorigenesis is poorly understood. Methods and Results Here, we have studied the somatic landscape of 3 different angiosarcoma patients with mutations in the POT1 gene to further investigate this tumorigenesis process. In addition, the genetic landscape of 7 CAS patients without mutations in the POT1 gene has been studied. Patients with CAS and nonfunctional POT1 did not repress ATR (ataxia telangiectasia RAD3‐related)–dependent DNA damage signaling and showed a constitutive increase of cell cycle arrest and somatic activating mutations in the VEGF (vascular endothelial growth factor)/angiogenesis pathway (KDR gene). The same observation was made in POT1 mutation carriers with tumors different from CAS and also in CAS patients without mutations in the POT1 gene but with mutations in other genes involved in DNA damage signaling. Conclusions Inhibition of POT1 function and damage‐response malfunction activated DNA damage signaling and increased cell cycle arrest as well as interfered with apoptosis, which would permit acquisition of somatic mutations in the VEGF/angiogenesis pathway that drives tumor formation. Therapies based on the inhibition of damage signaling in asymptomatic carriers may diminish defects on cell cycle arrest and thus prevent the apoptosis deregulation that leads to the acquisition of driver mutations.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2047-9980Test

الوصول الحر: https://doaj.org/article/798ab5626f524e1a8629eaa7135e8845Test