Identificación de novos biomarcadores de cardiotoxicidade en pacientes de cancro de mama

O cancro de mama (CM) é o cancro máis prevalente en mulleres en todo o mundo. Enfoques terapéuticos actuais, como cirurxía, terapia de radiación e/ou terapia sistémica son seleccionados en función do tamaño do tumor, o perfil de estróxenos, proxesterona e/ou do receptor HER2, a implicación dos ganglios linfáticos e a presenza ou ausencia de metástases. Na última década, a combinación terapéutica da cirurxía, radioterapia e quimioterapia supuxo un avance importante na supervivencia de pacientes con CM. Ademais, as melloras na detección precoz e a terapia resultaron nun aumento gradual dos taxas de supervivencia. Os sobreviventes do CM que viven máis tempo son gradualmente expostos aos efectos nefastos a longo prazo que se producen asociados á quimioterapia. A cardiotoxicidade (CT) é unha das complicacións máis comúns de terapias actuais do cancro. En consecuencia, a enfermidade cardiovasculares (CV) é a principal causa de morte entre os sobreviventes dos estadios iniciais de cancro de mama. A predisposición a CT é multifactorial e é determinada pola interacción entre factores xenéticos e ambientais. Aínda que a magnitude do problema non é clara, xa que só nalgúns casos se fixo un estudo prospectivo da función cardíaca, os datos acumulados en base a estudos retrospectivos mostran que é esencial considerar os factores de risco cardiovasculares e outras comorbidades pacientes específicos (por exemplo, idade, hipertensión, enfermidade vascular periférica, diabetes e enfermidade arterial coronaria preexistente). A susceptibilidade a CT pode impedir o acceso a un tratamento adecuado, a costa de un peor prognóstico. Ata hai pouco, o CT foi exclusivamente asociado co uso de antraciclinas; con todo, outras drogas citostáticas recentes de nova xeración tamén foron asociados coa toxicidade cardiovascular. Aínda que só foron realizados algúns estudos prospectivos débiles da función cardíaca debe ser confirmados a máis longo prazo, hai varios datos que mostran un amplo espectro de anormalidades cardiovasculares. O obxectivo deste estudo foi avaliar a toxicidade en células de sangue periférico (PBMC), ademais de marcadores biolóxicos ea súa correlación coa cambios funcionais ecocardiográficas durante o tratamento con citostático que pode dar o luxo de establecer o seu valor pronóstico/diagnóstico, ademáis de estudar o dano por taxanos nunha liña celular de cardiomiocitos e a cardioprotección protección por parte da omentina

Omentin protects H9c2 cells against docetaxel cardiotoxicity

Background : Association between obesity and cardiovascular diseases is well known, however increased susceptibility of obese patients to develop several cancer types is not so commonly known. Current data suggest that poorer overall survival in cancer patients might be associated to non-cancer-related causes such as higher risk of cardiotoxicity in obese patients treated with chemotherapeutic agents. Omentin, a novel adipokine decreased in obesity, is actually in the spotlight due to its favourable effects on inflammation, glucose homeostasis and cardiovascular diseases. Also, recent data showed that in vitro anthracycline-induced cardiomyocyte apoptosis is counteracted by omentin suggesting its cardioprotective role. Objective: Our aim was to evaluate omentin effects against docetaxel toxicity. Results: Our data indicate that omentin inhibits docetaxel-induced viability loss and that increased viability is associated to decreased caspase-3 expression and cell death. Although omentin reduces NOX4 expression, it failed to reduce docetaxel-induced reactive oxygen species production. Our results indicate that omentin decreases docetaxel-induced endoplasmic reticulum stress, suggesting that cardioprotective role might be associated to ERS inhibition. Conclusion : These data suggest that omentin treatment may contribute to decrease susceptibility to DTX-induced cardiotoxicity.This work was supported by Fundación Mutua Madrileña 2014 (R.L.), Red de Investigación Cardiovascular (RIC) (RD12/0042/0039) an initiative of ISCIII (J.R.G-J), Programa de Consolidación de Unidades de Investigación Competitivas do SUG (GPC 2013-051) of Xunta de Galicia (J.R.G-J) and Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV) (CB16/11/00226) of Instituto de Salud Carlos III (J.R.G-J). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscriptS

Bioelectronics-on-a-chip for cardio myoblast proliferation enhancement using electric field stimulation

Background: Cardio myoblast generation from conventional approaches is laborious and time-consuming. We present a bioelectronics on-a-chip for stimulating cells cardio myoblast proliferation during culture. Method: The bioelectronics chip fabrication methodology involves two different process. In the first step, an aluminum layer of 200 nm is deposited over a soda-lime glass substrate using physical vapor deposition and selectively removed using a Q-switched Nd:YVO4 laser to create the electric tracks. To perform the experiments, we developed a biochip composed of a cell culture chamber fabricated with polydimethylsiloxane (PDMS) with a glass coverslip or a cell culture dish placed over the electric circuit tracks. By using such a glass cover slip or cell culture dish we avoid any toxic reactions caused by electrodes in the culture or may be degraded by electrochemical reactions with the cell medium, which is crucial to determine the effective cell-device coupling. Results: The chip was used to study the effect of electric field stimulation of Rat ventricular cardiomyoblasts cells (H9c2). Results shows a remarkable increase in the number of H9c2 cells for the stimulated samples, where after 72 h the cell density double the cell density of control samples. Conclusions: Cell proliferation of Rat ventricular cardiomyoblasts cells (H9c2) using the bioelectronics-on-a-chip was enhanced upon the electrical stimulation. The dependence on the geometrical characteristics of the electric circuit on the peak value and homogeneity of the electric field generated are analyzed and proper parameters to ensure a homogeneous electric field at the cell culture chamber are obtained. It can also be observed a high dependence of the electric field on the geometry of the electrostimulator circuit tracks and envisage the potential applications on electrophysiology studies, monitoring and modulate cellular behavior through the application of electric fieldsThis work was partially supported by Mineco through the projects FIS 2015–71933-REDT and RTI 2018–097063-B-I00, Consellería de Educación Program for Development of a Strategic Grouping in Materials – AeMAT Grant No. ED431E2018/08, Xunta de Galicia ref. ED431B2017/64. Xunta de Galicia, Spain, under Galician Programme for Research Innovation and Growth 2011–2015 (I2C Plan)S

Plasma miR-486-5p Expression Is Upregulated in Atrial Fibrillation Patients with Broader Low-Voltage Areas

Atrial fibrillation (AF) is the most common arrhythmia worldwide, affecting 1% of the population over 60 years old. The incidence and prevalence of AF are increasing globally, representing a relevant health problem, suggesting that more advanced strategies for predicting risk stage are highly needed. miRNAs mediate several processes involved in AF. Our aim was to identify miRNAs with a prognostic value as biomarkers in patients referred for AF ablation and its association with LVA extent, based on low-voltage area (LVA) maps. In this study, we recruited 44 AF patients referred for catheter ablation. We measured the expression of 84 miRNAs in plasma from peripheral blood in 3 different groups based on LVA extent. Expression analysis showed that miR-486-5p was significantly increased in patients with broader LVA (4-fold, p = 0.0002; 5-fold, p = 0.0001). Receiver operating characteristic curve analysis showed that miR-486-5p expression could predict atrium LVA (AUC, 0.8958; p = 0.0015). Also, miR-486-5p plasma levels were associated with AF-type (AUC, 0.7137; p = 0.0453). In addition, miR-486-5p expression was positively correlated with LVA percentage, left atrial (LA) area, and LA volume (r = 0.322, p = 0.037; r = 0.372, p = 0.015; r = 0.319, p = 0.045, respectively). These findings suggest that miR-486-5p expression might have prognostic significance in LVA extent in patients with AFThis research was funded by Xunta de Galicia: Programa de Consolidación de Unidades de Investigación Competitivas do SUG (GRC 2019/02), the Centro Singular de Investigación de Galicia acreditación 2019–2022 (ED431G 2019/02), the European Union European Regional Development Fund (ERDF), and National Institute of Health Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III (ISCIII) Madrid, Spain (PI18/00821, CIBERCV CB16/11/00226 and FAISCA Intramural Project 2019)S

FNDC5/Irisin counteracts lipotoxic-induced apoptosis in hypoxic H9c2 cells

Irisin is a newly identified adipokine critical to modulate body metabolism, fatty acid metabolism and oxidative stress; recent evidence suggests a cardioprotective role in ischemic injury. Loss of cardiomyocytes during acute myocardial infarction is strongly associated with energetic changes and lipotoxic-induced apoptosis. Our aim was to study FNDC5/irisin's potential protective role against hypoxia and lipotoxicity, both related with myocardial infarction environment. H9c2 cells were treated with palmitate and/or irisin in normoxic/hypoxic conditions. Cell viability and apoptosis were assessed by MTT assay and annexin V/PI staining. Immunoblotting was used to confirm apoptotic cascade regulation. Irisin counteracts lipotoxic-induced apoptosis in hypoxic cardiomyoblasts by activating Akt signaling pathway suggesting the potential therapeutic role of irisin in ischemic heart disease

Circulating miR-451a Expression May Predict Recurrence in Atrial Fibrillation Patients after Catheter Pulmonary Vein Ablation

Atrial fibrillation is the most prevalent tachyarrhythmia in clinical practice, with very high cardiovascular morbidity and mortality with a high-cost impact in health systems. Currently, it is one of the main causes of stroke and subsequent heart failure and sudden death. miRNAs mediate in several processes involved in cardiovascular disease, including fibrosis and electrical and structural remodeling. Several studies suggest a key role of miRNAs in the course and maintenance of atrial fibrillation. In our study, we aimed to identify the differential expression of circulating miRNAs and their predictive value as biomarkers of recurrence in atrial fibrillation patients undergoing catheter pulmonary vein ablation. To this effect, 42 atrial fibrillation patients were recruited for catheter ablation. We measured the expression of 84 miRNAs in non-recurrent and recurrent groups (45.2%), both in plasma from peripheral and left atrium blood. Expression analysis showed that miRNA-451a is downregulated in recurrent patients. Receiver operating characteristic curve analysis showed that miR-451a in left atrium plasma could predict atrial fibrillation recurrence after pulmonary vein isolation. In addition, atrial fibrillation recurrence is positively associated with the increment of scar percentage. Our data suggest that miRNA-451a expression plays an important role in AF recurrence by controlling fibrosis and progression

Circulating miR-499a and miR-125b as Potential Predictors of Left Ventricular Ejection Fraction Improvement after Cardiac Resynchronization Therapy

Cardiac resynchronization therapy represents a therapeutic option for heart failure drug-refractory patients. However, due to the lack of success in 30% of the cases, there is a demand for an in-depth analysis of individual heterogeneity. In this study, we aimed to evaluate the prognostic value of circulating miRNA differences. Responder patients were defined by a composite endpoint of the presence of left ventricular reverse remodelling (a reduction ≥15% in telesystolic volume and an increment ≥10% in left ventricular ejection fraction). Circulating miRNAs signature was analysed at the time of the procedure and at a 6-month follow-up. An expression analysis showed, both at baseline and at follow-up, differences between responders and non-responders. Responders presented lower baseline expressions of miR-499, and at follow-up, downregulation of miR-125b-5p, both associated with a significant improvement in left ventricular ejection fraction. The miRNA profile differences showed a marked sensitivity to distinguish between responders and non-responders. Our data suggest that miRNA differences might contribute to prognostic stratification of patients undergoing cardiac resynchronization therapy and suggest that preimplant cardiac context as well as remodelling response are key to therapeutic success