Oxidative stress, defined as the excess production of reactive oxygen species (ROS) relative to antioxidant defense, plays a significant role in the development of cardiovascular diseases. Endoplasmic reticulum (ER) stress has emerged as an important source of ROS and its modulation could be cardioprotective. Previously, we demonstrated that miR-16-5p is enriched in the plasma of ischemic dilated cardiomyopathy (ICM) patients and promotes ER stress-induced apoptosis in cardiomyocytes in vitro. Here, we hypothesize that miR-16-5p might contribute to oxidative stress through ER stress induction and that targeting miR-16-5p may exert a cardioprotective role in ER stress-mediated cardiac injury. Analysis of oxidative markers in the plasma of ICM patients demonstrates that oxidative stress is associated with ICM. Moreover, we confirm that miR-16-5p overexpression promotes oxidative stress in AC16 cardiomyoblasts. We also find that, in response to tunicamycin-induced ER stress, miR-16-5p suppression decreases apoptosis, inflammation and cardiac damage via activating the ATF6-mediated cytoprotective pathway. Finally, ATF6 is identified as a direct target gene of miR-16-5p by dual-luciferase reporter assays. Our results indicate that miR-16-5p promotes ER stress and oxidative stress in cardiac cells through regulating ATF6, suggesting that the inhibition of miR-16-5p has potential as a therapeutic approach to protect the heart against ER and oxidative stress-induced injury.

Introducción: La población geriátrica es especialmente vulnerable a la enfermedad por coronavirus (COVID-19) y sus posibles complicaciones. Nos propusimos analizar la incidencia de complicaciones cardiológicas en una población anciana hospitalizada por COVID-19. Métodos: Estudio longitudinal observacional prospectivo que incluyó a pacientes ≥ 75 años con diagnóstico de COVID-19 ingresados en el Servicio de Geriatría de marzo a mayo de 2020. Se recogieron variables epidemiológicas, geriátricas, clínicas y de laboratorio. Se documentaron eventos cardiovasculares, que incluyen fibrilación auricular (FA) de novo, síndrome coronario agudo (SCA), insuficiencia cardíaca congestiva (ICC), embolia pulmonar y muerte intrahospitalaria. Se realizó un seguimiento a los 12 meses, mediante entrevista telefónica y accediendo a la historia clínica electronica, recogiendo eventos cardíacos y mortalidad. Resultados: Se incluyeron 305 pacientes; 190 (62,3%) eran mujeres, con una mediana de edad de 87 años (RIQ (82 - 91)). Más de la mitad de los pacientes tenían antecedentes de enfermedad cardíaca, siendo la FA la más frecuente y afectando a 85 (27,9%) pacientes. Durante la hospitalización fallecieron 112 (36,7%) pacientes. Ochenta y nueve (29,2%) pacientes presentaron complicaciones cardíacas. La ICC aguda fue la más prevalente (46; 15,1%), seguida de la FA de nueva aparición (20; 6,5%), la embolia pulmonar (17; 5,6%) y el SCA (5; 1,6%). Los pacientes con complicaciones cardíacas tuvieron una estancia hospitalaria más prolongada (p <0,001). Durante el seguimiento fallecieron 29 pacientes (15,1%) y 40 (20,8%) pacientes presentaron un evento cardiovascular, siendo la ICC la complicación más prevalente (16,7%). Conclusión: La incidencia de complicaciones cardiovasculares en pacientes geriátricos es alta y se asocia a una mayor estancia hospitalaria. La insuficiencia cardíaca congestiva fue el evento más frecuente, seguida de la FA.

Dilated cardiomyopathy (DCM) is a clinical diagnosis characterized by left ventricular or biventricular dilation and systolic dysfunction. In most cases, DCM is progressive, leading to heart failure (HF) and death. This cardiomyopathy has been considered a common and final phenotype of several entities. DCM occurs when cellular pathways fail to maintain the pumping function. The etiology of this disease encompasses several factors, such as ischemia, infection, autoimmunity, drugs or genetic susceptibility. Although the prognosis has improved in the last few years due to red flag clinical follow-up, early familial diagnosis and ongoing optimization of treatment, due to its heterogeneity, there are no targeted therapies available for DCM based on each etiology. Therefore, a better understanding of the mechanisms underlying the pathophysiology of DCM will provide novel therapeutic strategies against this cardiac disease and their different triggers. MicroRNAs (miRNAs) are a group of small noncoding RNAs that play key roles in post-transcriptional gene silencing by targeting mRNAs for translational repression or, to a lesser extent, degradation. A growing number of studies have demonstrated critical functions of miRNAs in cardiovascular diseases (CVDs), including DCM, by regulating mechanisms that contribute to the progression of the disease. Herein, we summarize the role of miRNAs in inflammation, endoplasmic reticulum (ER) stress, oxidative stress, mitochondrial dysfunction, autophagy, cardiomyocyte apoptosis and fibrosis, exclusively in the context of DCM.