RESUMEN
INTRODUCTION: Cardiac remodeling is defined as cellular interstitial changes that lead dysfunction of the heart after injury. Placental growth factor (PlGF), a member of the VEGF family, has been reported to regulate cardiac hypertrophy in hemodynamic state. We therefore analyze the function of PlGF during cardiac remodeling using cardiac cells and fibroblasts, under Angiotensin II (AngII) stimulation. METHODS: PlGF overexpressed mouse embryonic fibroblasts derived from C57BL/6 mice, were made by deficient retrovirus vector, designated as C57/PlGF. Only retrovirus vector introduced C57 cells (C57/EV) were used as control. After AngII stimulation, wound scratching assay and MTT proliferation assay with or without p38 MAPK inhibitor, SB205580 were performed in retrovirally-introduced C57 cells. Reactive oxygen species (ROS) production, NF-kB activation, IL-6 and TNF-α production were also measured. Then we assessed AngII-induced cell proliferation of mouse cardiac fibroblasts (CFs) and rat primary cardiomyocytes incubating with C57/PlGF conditioned-medium. RESULTS: The PlGF production in C57/PlGF were confirmed by ELISA (1093.48 ± 3.5 pg/ml, ±SE). AngII-induced cell migration, proliferation and H2O2 production were increased in C57/PlGF compared with C57/EV. SB205580 inhibited the AngII-induced cell proliferation in C57/PlGF. In C57/PlGF cells, NF-kB activation was higher, followed by up-regulation of IL-6 and TNF-α production. CFs and cardiomyocytes proliferation increased when stimulated with C57/PlGF conditioned-medium. DISCUSSION: The activation of fibroblast is stimulated by PlGF signaling via p38 MAPK/NF-kB pathway accompanied by elevation of ROS and inflammatory response. Furthermore, these signals stimulate the activation of CFs and cardiomyocytes, indicating that high circulating level of PlGF have a potential to regulate cardiac remodeling.
Asunto(s)
Angiotensina II , Proliferación Celular , Fibroblastos , Ratones Endogámicos C57BL , Miocitos Cardíacos , Factor de Crecimiento Placentario , Especies Reactivas de Oxígeno , Remodelación Ventricular , Animales , Factor de Crecimiento Placentario/metabolismo , Fibroblastos/metabolismo , Ratones , Ratas , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/efectos de los fármacos , Angiotensina II/farmacología , Remodelación Ventricular/fisiología , Proliferación Celular/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , FN-kappa B/metabolismo , Proteínas Gestacionales/metabolismo , Transducción de Señal , Movimiento Celular/efectos de los fármacos , Femenino , Células Cultivadas , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Interleucina-6/metabolismoAsunto(s)
Enfermedad de la Arteria Coronaria , Placa Aterosclerótica , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológicoRESUMEN
We describe the case of a 21-year-old patient who underwent repairs for multiple lesions including aortic and pulmonary valve replacements, right ventricular outflow tract reconstruction, revision of the right pulmonary artery route, and a repair of partial anomalous pulmonary venous drainage, which was diagnosed during this fourth sternotomy. For these patients with adult CHD, it is most important to address all underlying factors as much as possible at the redo surgery.