Vascular smooth muscle cell phenotype is modulated by ligands of the lymphotoxin beta receptor and the tumor necrosis factor receptor / El fenotipo de las células de músculo liso vascular es modulado por los ligandos del receptor de la linfotoxina beta y del receptor del factor de necrosis tumoral

Objective: Vascular smooth muscle cells (VSMCs) undergo a phenotypic-switching process during the generation of unstable atheroma plaques. In this investigation, the potential implication of the tumor necrosis factor superfamily (TNFSF) ligands, in the gene expression signature associated with VSMC plasticity was studied. Material and methods: Human aortic (ha)VSMCs were obtained commercially and treated with the cytokine TNFSF14, also called LIGHT, the lymphotoxin alpha (LTα), the heterotrimer LTα1β2 or with vehicle for 72h. The effect of the different treatments on gene expression was analyzed by quantitative PCR and included the study of genes associated with myofibroblast-like cell function, osteochondrogenesis, pluripotency, lymphorganogenesis and macrophage-like cell function. Results: HaVSMCs displayed a change in myofibroblast-like cell genes which consisted in reduced COL1A1 and TGFB1 mRNA levels when treated with LTα or LIGHT and with augmented MMP9 expression levels when treated with LTα. LTα and LIGHT treatments also diminished the expression of genes associated with osteochondrogenesis and pluripotency SOX9, CKIT, and KLF4. By contrary, all the above genes were no affected by the treatment with the trimer LTα1β2. In addition, haVSMC treatment with LTα, LTα1β2 and LIGHT altered lymphorganogenic cytokine gene expression which consisted of augmented CCL20 and CCL21 mRNA levels by LTα and a reduction in the gene expression of CCL21 and CXCL13 by LIGHT and LTα1β2 respectively. Neither, LTα or LIGHT or LTα1β2 treatments affected the expression of macrophage-like cell markers in haVSMC. Conclusions: Altogether, indicates that the TNFSF ligands through their interconnected network of signaling, are important in the preservation of VSMC identity against the acquisition of a genetic expression signature compatible with functional cellular plasticity.(AU)

Objetivo: La transición de placa de ateroma estable a placa inestable implica, entre otros procesos, un cambio fenotípico de las células del músculo liso vascular (CMLVs). En esta investigación, se estudió el posible papel de los ligandos de la superfamilia del factor de necrosis tumoral (TNFSF), en los cambios de expresión génica asociada a la plasticidad de las CMLVs. Materiales y métodos: Las CMLVs de aorta humana (CMLVah) se obtuvieron comercialmente y se trataron con la citoquina TNFSF14, también llamada LIGHT, la linfotoxina alfa (LTα), el heterotrímero LTα1β2 o con vehículo durante 72 horas. El efecto de los diferentes tratamientos se analizó mediante el estudio de la expresión génica por PCR cuantitativa e incluyó genes asociados con fenotipo miofibroblástico, osteocondrogénico, genes de pluripotencia, genes de linforganogénesis y genes característicos de macrófagos. Resultados: El estudio de genes asociados a fenotipo miofibroblástico en las CMLVah reveló una reducción de la expresión génica de COL1A1 y TGFB1 tras el tratamiento con LTα o LIGHT mientras que el tratamiento con LTα aumentó los niveles de mRNA de MMP9. LTα y LIGHT también disminuyeron la expresión de genes de osteocondrogénesis y pluripotencia como SOX9, CKIT y KLF4. Por el contrario, la expresión de los genes anteriores no se vio afectada por el tratamiento con el trímero LTα1β2. El tratamiento de las CMLVah con LTα, LTα1β2 y LIGHT alteró la expresión génica de citoquinas linforganogénicas con una expresión aumentada de los genes CCL20 y CCL21 por LTα y una reducción de los niveles de mRNA de CCL21 y CXCL13 por LIGHT y LTα1β2, respectivamente. Ninguno de los tres tratamientos alteró la expresión de genes típicos de macrófagos en las CMLVah. Conclusiones: La presente investigación indica que los ligandos de la familia de los TNFSF a través de su red de señalización...(AU)

Adiponectin overexpression in C2C12 myocytes increases lipid oxidation and myofiber transition

Metabolic syndrome and obesity have detrimental effects on the metabolic function of the skeletal muscle. Mounting evidence indicates that patients with those conditions may present an increased ratio of glycolytic to oxidative fibers associated with a decrease in oxidative capacity. In this regard, adiponectin, a hormone mainly secreted by adipocytes that regulates glucose and lipid metabolism, has emerged as a myokine that could play an important role in this process. We aimed to investigate whether adiponectin overexpression in skeletal muscle might be a local protective mechanism, favoring fatty acid utilization. To that end, we generated an in vitro model of myocytes with upregulated endogenous adiponectin using a lentiviral carrier. We demonstrated that the adiponectin-transduced myocytes were able to produce and secrete fully functional adiponectin complexes. Adiponectin overexpression remarkably upregulated the mRNA level of myogenic regulatory factors as well as genes implicated in lipolysis (HSL, ATGL) and cellular and mitochondrial fatty acid transport (LPL, CD36, CPT1B). This was accompanied by increased isoproterenol-induced lipolysis and β-oxidation and reduced lipogenesis, whereas insulin-stimulated glucose uptake was unaltered in transduced myocytes. Lastly, the relative expression of the more glycolytic myofibers (MyHC IIb) compared to the more oxidative ones (MyHC I) was notably reduced. Our results showed that the released adiponectin acted in an autocrine/paracrine manner, increasing lipid oxidation in myocytes and leading to a transition of myofibers from the glycolytic to the oxidative type. In conclusion, muscle adiponectin overexpression might be a way to relieve muscle diseases caused by oxidative muscle fiber deficiency. (AU)

Métodos de evaluación de la masa muscular: una revisión sistemática de ensayos controlados aleatorios / Methods of evaluation of muscle mass: a systematic review of randomized controlled trials

Introducción: en los últimos años las investigaciones sobre la masa muscular han cobrado popularidad por su relación con la salud. Así, la medición precisa de la masa muscular puede tener aplicación clínica, ya que puede interferir en el diagnóstico y prescripción del tratamiento medicamentoso o no medicamentoso. Objetivo: realizar una revisión sistemática de los métodos más utilizados para la evaluación de la masa muscular en ensayos controlados aleatorios, con sus ventajas y desventajas. Método: se llevó a cabo una búsqueda en las bases de datos Pubmed, Web of Science y Scopus, con las palabras muscle mass, measurement, assessment y evaluation, combinadas de esta manera: 'muscle mass' AND (measurement OR assessment OR evaluation). Resultados: 23 estudios fueron recuperados y analizados, todos ellos en inglés. El 69,56% utilizaron solamente un método para la cuantificación de la masa muscular; el 69,57% utilizaron la doble absorciometría de rayos X (DXA); en el 45,46% el tipo de medida utilizado fue la masa corporal total libre de grasa; y el 51,61% eligieron el cuerpo total como sitio de medida. Conclusiones: en los ensayos controlados aleatorios analizados la mayor parte utilizó apenas un método de evaluación, siendo la DXA el método más empleado, la masa corporal total libre de grasa el tipo de medida más utilizado y el cuerpo total el sitio de medida más común (AU)

Introduction: in recent years, research about muscle mass has gained popularity for their relationship to health. Thus precise measurement of muscle mass may have clinical application once may interfere with the diagnosis and prescription drug or drug treatment. Objective: to conduct a systematic review of the methods most used for evaluation of muscle mass in randomized controlled trials, with its advantages and disadvantages. Methods: we conducted a search of the data bases PubMed, Web of Science and Scopus, with words 'muscle mass', 'measurement', 'assessment' and 'evaluation', combined in this way: 'muscle mass' AND (assessment OR measurement OR evaluation). Results: 23 studies were recovered and analyzed, all in English. 69.56% only used a method for quantification of muscle mass; 69.57% used dual X-ray absorptiometry (DXA); in 45.46% the type of measure used was the body lean mass; and 51.61% chose the whole body as a site of measurement. Conclusions: in the randomized controlled trials analyzed the majority used just one method of assessment, with the DXA being the method most used, the body lean mass the measurement type most used and total body the most common site of measure (AU)

The influence of short-term L-arginine supplementation on rats' muscular and hepatic cells in ischemia-reperfusion syndrome

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Due to the complex mechanisms of L-arginine activity, it is difficult to determine the clinical significance of supplementation with this amino acid. The objective of this study was to determine the influence of short-term supplementation with L-arginine in stress conditions, induced by ischemia-reperfusion syndrome, by assessing the damage to muscular and hepatic cells on the basis of creatine kinase (CK), alanine aminotransferase (ALAT) and aspartic aminotransferase (AspAT) activity in blood and the level of oxygen free radicals in analyzed tissues of rats. We observed that induced ischemia of hind limb caused an increase in CK, ALAT and AspAT activity and an increase in the level of free radicals in liver, but not in skeletal muscle. Supplementation withL-arginine led to a reduction in serum activity of CK and AspAT and reduction of the level of free radicals in analysed tissues. Simultaneous supplementation with L-arginine AND L-NAME resulted in a reversal of changes induced by L-arginine supplementation in the case of AspAT and free radicals in skeletal muscle. The results indicate that under conditions of ischemia-reperfusion, short-term administration of L-arginine has a protective effect on skeletal muscle manifesting itself by reduction of CK in the serum and reduction of free radicals level in THIS tissue (AU)

Solución del caso 37. Rabdomiólisis por cocaína / Solution to case 37. Cocaine-induced rhabdomyolysis

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Treadmill exercise suppresses muscle cell apoptosis by increasing nerve growth factor levels and stimulating p-phosphatidylinositol 3-kinase activation in the soleus of diabetic rats

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We investigated the effects of treadmill exercise performed regularly for 6 weeks on the levels of nerve growth factor (NGF), tyrosine kinase A and p75 receptors, phosphatidylinositol 3-kinase (PI3-K), mitogen-activated protein kinase/extracellular signal-regulated kinase (Erk) 1,2, cyclic AMP response element-binding protein (CREB), and caspase-3 in the soleus of rats with streptozotocin (STZ)-induced diabetes. Thirty-two male Sprague–Dawley rats were divided into the following four groups: (1) normal control group (NCG; n = 8), (2) normal exercise group (NEG; n = 8), (3) diabetes control group (DCG; n = 8), and (4) diabetes exercise group (..) (AU)

Distrofias musculares de cinturas autosómicas recesivas / Autosomal recessive limb-girdle muscular dystrophy

Resumen. Las distrofias musculares son un grupo heterogéneo de enfermedades hereditarias, caracterizadas por debilidad y pérdida muscular de origen no neurogénico. Son causadas por mutaciones de uno o más genes involucrados en la formación de las células musculares. El descubrimiento de las diversas proteínas presentes en el músculo comenzó con el descubrimiento de la distrofina, 130 años después de la descripción clínica de la distrofia muscular. Actualmente, debido al mejor conocimiento de la biología del músculo normal y del enfermo, se ha logrado realizar una clasificación molecular de los diferentes tipos de distrofias musculares, de acuerdo con la proteína que se encuentre afectada. Esto ha sido particularmente importante para las distrofias musculares de cinturas, las cuales presentan características clínicas que pueden llevar a confundirlas con la distrofia muscular de Duchenne. Por otro lado, en años recientes se ha favorecido el desarrollo de terapias que en un futuro cercano podrían dar una solución para la restauración de la función de la fibra muscular (AU)

Summary. Muscular dystrophies are a heterogeneous group of hereditary diseases characterized by loss of muscle and weakness of non neurogenic origin. They are caused by mutations in one or more genes involved in the formation of muscle cells. The discovery of several proteins in the muscle began with the discovery of dystrophin, 130 years after the clinical description of muscular dystrophy. Currently, due to a better understanding of the biology of normal and diseased muscle, has achieved a classification at the molecular level of different types of muscular dystrophies, according to the protein that is affected. This has been particularly important for limb girdle muscular dystrophies, which present clinical features that can lead to confusion with Duchenne muscular dystrophy. Moreover, in recent years has encouraged the development of therapies in the near future could provide a solution for restoring the function of the muscle fiber (AU)

Células madre derivadas de músculo para la incontinencia urinaria de esfuerzo / Muscle-derived stem cell therapy for stress urinary incontinence

El conocimiento de la incontinencia urinaria de esfuerzo (IUE) se ha incrementado, dando como resultado una amplia gama de diferentes opciones terapéuticas disponibles. La uretra media y el esfínter uretral externo son ahora el eje en el manejo de la IUE. La terapia con células madre para la regeneración del esfínter deficiente ha sido motivo de investigaciones novedosas. Obteniendo mioblastos y fibroblastos autólogos de biopsias musculares esqueléticas, cultivándolas e implantándolas después de su diferenciación en el esfínter uretral externo se advierte un nuevo concepto en el tratamiento de la incontinencia de esfuerzo. En lugar de utilizar materiales heterólogos, tales como mallas sintéticas (slings) o sustancias de abultamiento (colágeno, siliconas, etc.), ahora tenemos el potencial para restaurar la función con el uso de células madre autólogas(AU)

The knowledge of the urinary effort incontinence (UEI) has increased, giving like result an ample range of different therapeutic options available. The middle urethra and external urethral sphincter are the focus in management of UEI. Stem cells therapy for the regenerative repair of the deficient sphincter has been the leading research of incontinence. Obtaining autologous myoblasts and fibroblasts of skeletal muscle-biopsies, cultivating them and transplanting them after its differentiation, into the external urethral sphincter it warns a new concept in the treatment of the incontinence. Instead of using heterologous materials such as synthetic mesh (slings) or bulking agents (collagen, silicone, etc); we now have the potential to restore function with the use of autologous stem cells(AU)

Efecto de la LDL modificada en la expresión de adipofilina en macrófagos y células musculares lisas de la pared vascular. Implicaciones para el desarrollo de arteriosclerosis / Effect of modified LDL in the expression of adipocyte differentiation-related protein in macrophages and vascular smooth muscle cells. Implications for atherosclerosis progression

Objetivo: Analizar si la unión e interiorización de la LDL modificada por agregación (LDLag) puede inducir la expresión de la proteina adipofilina (ADRP), un marcador de acumulación lipídica, en las células musculares lisas de la pared vascular (CMLV) y macrófagos humanos. Resultados: La LDLag induce la sobreexpresión de ADRP tanto a nivel de ARNm (PCR tiempo real) como a nivel de proteina («western blot») en CMLV (ARNm: 3.06-veces; proteina: 8.58-veces) y también en macrófagos (ARNm: 3.5-veces; proteina: 3.71-veces). Los estudios immunohistoquímicos evidenciaron una alta colocalización entre ADRP y CMLV y también entre ADRP y macrófagos en placas ateroscleróticas avanzadas ricas en lípido. Conclusiones: La captación de LDLag mediante el receptor lipoproteíco LRP1 juega un papel primordial en la formación de células espumosas a partir de macrófagos y de CMLV y, por tanto, en la progresión de la lesión aterosclerótica (AU)

Aims: The objectives of this work were to analyze whether aggregated LDL (agLDL) uptake modulates ADRP expression levels in human vascular smooth muscle cells (VSMC) and macrophages (HMDM). Methods and Results: AgLDL strongly upregulated ADRP mRNA (Real-time PCR) and protein expression (western blot) in human VSMC (mRNA: by 3.06-fold; protein: 8.58-fold) and HMDM (mRNA: by 3.5-fold; protein: by 3.71-fold).. Immunohystochemical studies evidence a high colocolocalization between ADRP/macrophages and ADRP/VSMC in advanced lipid-enriched atherosclerotic plaques. Conclusions:These results demonstrate that agLDL-LRP1 engagement induces ADRP overexpression in both HMDM and human VSMC. ADRP is highly expressed in advanced lipid-enriched human atherosclerotic plaques. Therefore, LRP1-mediated agLDL uptake might play a pivotal role on vascular foam cell formation and atherosclerotic plaque progression (AU)