miR-27a protects human mitral valve interstitial cell from TNF-α-induced inflammatory injury via up-regulation of NELL-1.

MicroRNAs (miRNAs) have been reported to be associated with heart valve disease, which can be caused by inflammation. This study aimed to investigate the functional impacts of miR-27a on TNF-α-induced inflammatory injury in human mitral valve interstitial cells (hMVICs). hMVICs were subjected to 40 ng/mL TNF-α for 48 h, before which the expressions of miR-27a and NELL-1 in hMVICs were altered by stable transfection. Trypan blue staining, BrdU incorporation assay, flow cytometry detection, ELISA, and western blot assay were performed to detect cell proliferation, apoptosis, and the release of proinflammatory cytokines. We found that miR-27a was lowly expressed in response to TNF-α exposure in hMVICs. Overexpression of miR-27a rescued hMVICs from TNF-α-induced inflammatory injury, as cell viability and BrdU incorporation were increased, apoptotic cell rate was decreased, Bcl-2 was up-regulated, Bax and cleaved caspase-3/9 were down-regulated, and the release of IL-1ß, IL-6, and MMP-9 were reduced. NELL-1 was positively regulated by miR-27a, and NELL-1 up-regulation exhibited protective functions during TNF-α-induced cell damage. Furthermore, miR-27a blocked JNK and Wnt/ß-catenin signaling pathways, and the blockage was abolished when NELL-1 was silenced. This study demonstrated that miR-27a overexpression protected hMVICs from TNF-α-induced cell damage, which might be via up-regulation of NELL-1 and thus modulation of JNK and Wnt/ß-catenin signaling pathways.

miR-27a protects human mitral valve interstitial cell from TNF-alpha-induced inflammatory injury via up-regulation of NELL-1

MicroRNAs (miRNAs) have been reported to be associated with heart valve disease, which can be caused by inflammation. This study aimed to investigate the functional impacts of miR-27a on TNF-α-induced inflammatory injury in human mitral valve interstitial cells (hMVICs). hMVICs were subjected to 40 ng/mL TNF-α for 48 h, before which the expressions of miR-27a and NELL-1 in hMVICs were altered by stable transfection. Trypan blue staining, BrdU incorporation assay, flow cytometry detection, ELISA, and western blot assay were performed to detect cell proliferation, apoptosis, and the release of proinflammatory cytokines. We found that miR-27a was lowly expressed in response to TNF-α exposure in hMVICs. Overexpression of miR-27a rescued hMVICs from TNF-α-induced inflammatory injury, as cell viability and BrdU incorporation were increased, apoptotic cell rate was decreased, Bcl-2 was up-regulated, Bax and cleaved caspase-3/9 were down-regulated, and the release of IL-1β, IL-6, and MMP-9 were reduced. NELL-1 was positively regulated by miR-27a, and NELL-1 up-regulation exhibited protective functions during TNF-α-induced cell damage. Furthermore, miR-27a blocked JNK and Wnt/β-catenin signaling pathways, and the blockage was abolished when NELL-1 was silenced. This study demonstrated that miR-27a overexpression protected hMVICs from TNF-α-induced cell damage, which might be via up-regulation of NELL-1 and thus modulation of JNK and Wnt/β-catenin signaling pathways.

Ejercicio y síndrome de falla cardíaca / Exercise and heart failure syndrome

El síndrome de falla cardíaca está aumentado su frecuencia, genera gran morbimortalidad y sus principales síntomas son fatiga, disnea e intolerancia al ejercicio. El entrenamiento aeróbico, el de fuerza o el combinado tienen beneficios sobre la patogénesis, síntomas específicos, tolerancia al ejercicio, capacidad física, fuerza muscular, pronóstico y calidad de vida y aapectos psicosociales de los pacientes. Cada vez aparecen meta-análisis y más estudios con buen diseño metodológico que reportan disminución de las admisiones hospitalarias, tiempo de hospitalizción, disminución de los costos, mejoría de los síntomas y efectos adversos y reducción de la mortalidad. El entrenamiento regular se asocia con múltiples adaptaciones centrales y periféricas explicadas por mecanismos claros que explican la mejoría del paciente con síndrome de falla cardíaca; entre ellos están el cambio de la función cardíaca, vascular, neurohumoral, muscular, inflamatoria. El ejercicio adecuadamente prescrito es seguro y eficaz en todos los estadios del síndrome de falla cardíaca.

The heart failure syndrome is increasing its frequency, it generates high morbidity and its main symptoms are fatigue, dyspneam and exercise intolerance. The aerobic training, resistance training, resistance training or the combined has benefits on the pathogenesis, specific symptoms, exercise tolerance, physical fitness, muscle strength, prognosis and quality of life and psychosocial aspects of patients. The meta-analysis and studies with good methodological design reported decreased hospital admissions, length of hospitalization, reduce costs, improvement of symptoms and adverse effects and mortality. Regular training is associated with multiple cantral and peripheral adaptations explained by clear mechanisms explaining the improvement in the patient with heart failure syndrome; among them are change in cardiac function, vascular, neurohumoral, muscular, inflammatory, so on, the properly prescribed exercise is safe and effective in all stages of the heart failure syndrome.

Anestesia para gestante cardiopata / Anaesthesia for pregnant cardiac disease

Gestantes com doença cardíaca habitualmente possuem prognóstico favorável tanto materno quanto fetal. Com exceção das pacientes com a síndrome de Eisenmenger, hipertensão pulmonar primária e síndrome de Marfan com aortopatia, morte materna durante a gravidez em pacientes cardiopatas é rara. A gravidez por si só impõe modificações hemodinâmicas significativas, colocando à prova o sistema cardiovascular. Doença cardíaca reumática é a mais frequente nas gestantes, e o edema agudo pulmonar, a complicação mais comum. Defeito do septo atrial é a cardiopatia congênita acianótica mais prevalente na população adulta, enquanto que a Tetralogia de Fallot é a mais frequente das cardiopatias congênitas cianóticas. Gravidez e cardiopatia são uma associação de grandes desafios para o anestesiologista. Para evitar complicações decorrentes da morbidade ou mortalidade materno-fetal, o anestesiologista deve conhecer a evolução da doença durante a gravidez. Aqui são discutidas a fisiopatologia, apresentação clínica e a condução anestésica das doenças cardíacas valvulares adquiridas, das doenças cardíacas congênitas, da doença isquêmica do miocárdio e das miocardiopatias na gravidez.

Pregnancy in most women with heart disease has a favorable maternal and fetal outcome. With the exception of patients with Eisenmenger syndrome, pulmonary hypertension primary, and Marfan syndrome with aortopathy, maternal death during pregnancy in women with heart disease is rare. Pregnancy per se imposes significant hemodynamic changes placing a major burden on the cardiovascular system. Rheumatic heart disease remains the most frequent heart disease in the pregnant population and the pulmonary edema is the most frequent complication. Atrial septal defect is the most frequent congenital acianotic heart disease in the adult population, whereas tetralogy of Fallot is the most common cyanotic congenital heart disease. Pregnancy and heart disease present a unique challenge to the anesthesiologist. To avoid untoward complications resulting in significant maternal and/or fetal morbidity or mortality, the anesthesiologist must be familiar about the progression of heart disease during pregnancy. In this article, we review the pathophysiology, clinical presentation, and anesthetic management of valvular, congenital, vascular and ischemic heart disease, and cardiomyopathy in pregnancy.

[Stentless bioprostheses they are better?]. / Las bioprótesis sin soporte, son mejores?

The history and evolution of the bioprostheses is revised, above all the stentless. According to the international literature these were the first prosthesis that were established to cardiac level with very good results in the haemodynamic aspect, but that to lack an adequate preparation to diminish its antigenicity, to enlarge its resistance and to avoid the deterioration by calcification, less lasting than the mechanics did them. Nevertheless, it given that the real valvular area is much better than in all the other prostheses, their magnificent haemodynamic performance, the not mandatory use of anticoagulants, they do it a good offering for the patients with valvulopathy, above all the aortic. That international experience, now also shows how the use of anticalcification has improved even more the performance of these prostheses, to enlarge considerably its useful time of long-term life, reasons these by that are being utilized in form increasingly more extensive, above all indicating its use in patients more young, which before was almost prohibitive. Finally the initial experience with these bioprotheses in the National Institute of Cardiology of México is mentioned.

Modificaciones del perfil lipídico en pacientes con diagnóstico reciente de hipertensión arterial, tratados con 80 mg/día de valsartán / Lipid modifications in patients with recently diagnosed high blood pressure of who were treated with 80 mg/día of valsartan

Los niveles de lípidos elevados en sangre representan un importante factor de riesgo modificable en la aparición de enfermedad coronaria en pacientes con hipertensión arterial (3). Contar con fármacos que además de ejercer su acción antihipertensiva puedan también mejorar los niveles de los lípidos en sangre, deberían ser el norte de las nuevas investigaciones en esta área. En este estudio evaluamos la modificación del perfil lipídico en pacientes con hipertensión arterial en estadio I y II, tratados con valsartán, un antagonista de los receptores AT1 de la Angiotensina II. Se realizó un estudio prospectivo en 28 pacientes de ambos sexos, con edad promedio de 40,2 años y diagnóstico inicial de Hipertensión Arterial. Se incluyeron únicamente pacientes con Hipertensión Arterial en Estadio I y II. Se realizó perfil lipídico, al inicio y tres meses después de tratamiento con 80 mg/día de valsartán. El perfil lipídico inicial indicó que más del 50 por ciento de los pacientes tenían asociada una hiperlipidemia. Tres meses después del tratamiento se observó una reducción estadísticamente significativa de Colesterol Total (p=0,0037) y de LDL (p=0,0030) al igual que las relaciones Colesterol total/HDL y LDL/HDL (p=0,000298 y p=0,000894 respectivamente). Puede recomendarse el uso de valsartán como droga hipotensora en pacientes con diagnóstico inicial de Hipertensión Arterial Sistémica, sobre todo de aquellos que presenten asociados, niveles elevados de lípidos en sangre, especialmente el colesterol total, la LDL y las relaciones colesterol total/HDL y LDL/HDL, con lo que se reduciría el riesgo de enfermedad cardiovascular

Lipid extraction attenuates the calcific degeneration of bovine pericardium used in cardiac valve bioprostheses.

Bovine pericardial bioprostheses frequently fail due to dystrophic calcification. Since (a) recent studies indicate that membrane-associated complexed acidic phospholipids play an important role in the process of both physiologic and pathologic calcification, and (b) cytoplasmic organelles and plasma membrane of interstitial cells seem to serve as initial sites of calcific degeneration of bioprosthetic bovine pericardial tissue, this investigation was undertaken to evaluate whether, and if so, to what extent, the mineralization of valve tissue could be attenuated by previous lipid extraction. Pretreatment of glutaraldehyde-preserved bovine pericardium with acidified sulphuric ether (pH 3.0-4.0) attenuated calcification significantly: 28 days after subcutaneous implantation in young rats the degree of mineral deposition was approximately equal to typical 7 days implants in this model. The mechanism of this beneficial effect is suggested to be due to partial extraction of tissue phospholipids, as demonstrated by electron microscopy, thus reducing the number of available sites for deposition of hydroxyapatite crystals. In addition, and importantly, the present results indicate that any attempt to reduce cardiac valve bioprosthesis mineralization will have to take into account the role of lipids and, particularly, the membranous phospholipids in the calcification mechanism.