RESUMEN
BACKGROUND: Heart failure (HF) is a complex syndrome associated with a maladaptive innate immune system response that leads to deleterious cardiac remodeling. However, the underlying mechanisms of this syndrome are poorly understood. Nucleotide-binding oligomerization domain-containing protein 1 (NOD1) is a newly recognized innate immune sensor involved in cardiovascular diseases. OBJECTIVES: This study evaluated the role of NOD1 in HF progression. METHODS: NOD1 was examined in human failing myocardium and in a post-myocardial infarction (PMI) HF model evaluated in wild-type (wt-PMI) and Nod1-/- mice (Nod1-/--PMI). RESULTS: The NOD1 pathway was up-regulated in human and murine failing myocardia. Compared with wt-PMI, hearts from Nod1-/--PMI mice had better cardiac function and attenuated structural remodeling. Ameliorated cardiac function in Nod1-/--PMI mice was associated with prevention of Ca2+ dynamic impairment linked to HF, including smaller and longer intracellular Ca2+ concentration transients and a lesser sarcoplasmic reticulum Ca2+ load due to a down-regulation of the sarcoplasmic reticulum Ca2+-adenosine triphosphatase pump and by augmented levels of the Na+/Ca2+ exchanger. Increased diastolic Ca2+ release in wt-PMI cardiomyocytes was related to hyperphosphorylation of ryanodine receptors, which was blunted in Nod1-/--PMI cardiomyocytes. Pharmacological blockade of NOD1 also prevented Ca2+ mishandling in wt-PMI mice. Nod1-/--PMI mice showed significantly fewer ventricular arrhythmias and lower mortality after isoproterenol administration. These effects were associated with lower aberrant systolic Ca2+ release and with a prevention of the hyperphosphorylation of ryanodine receptors under isoproterenol administration in Nod1-/--PMI mice. CONCLUSIONS: NOD1 modulated intracellular Ca2+ mishandling in HF, emerging as a new target for HF therapy.
Asunto(s)
Calcio/metabolismo , Insuficiencia Cardíaca/metabolismo , Proteína Adaptadora de Señalización NOD1/fisiología , Animales , Arritmias Cardíacas/metabolismo , Calcio/fisiología , Progresión de la Enfermedad , Humanos , Ratones , Miocardio/metabolismo , Miocitos Cardíacos/metabolismo , Proteína Adaptadora de Señalización NOD1/metabolismo , Canal Liberador de Calcio Receptor de Rianodina/metabolismo , Retículo Sarcoplasmático/metabolismo , Regulación hacia ArribaRESUMEN
The spermogram is the simplest and the most important diagnostic to iniciate studies of male fertility. We are able to assess physical aspects such as volume, pH, mucus, viscosity, colour, and odour as well as cellular aspects related to the spermatozoids such as their number, mobility, morphology, and vitality. In addition, it provide us with valuable information as to the presence and characteristics of other cells such as macrophages, lymphocytes, leucocytes, bacteria, and fungi. The seminal fluid produced by the accessory sexual glands may also be evaluated by biochemical and immunological means.
El espermograma es el examen de diagnóstico más importante y sencillo para iniciar el estudio de la fertilidad masculina. En él se evaluán los aspectos físicos del semen, como el volumen, pH, mucólisis, viscosidad, color y olor y los aspectos celulares que estudia el espermatozoide en relación con el número, movilidad, morfología y vitalidad. También ofrece información valiosa sobre la presencia de otras células como macrófagos, linfocitos, leucocitos, bacterias y hongos. El líquido seminal que es producido por las glándulas sexuales anexas puede ser evaluado además desde el punto de vista bioquímico e inmunológico.
