RESUMEN
The present study aimed to test the hypothesis that increased sodium concentration affects the migratory phenotype of vascular smooth muscle cells (VSMCs) independently of the haemodynamic factors. Cell migration was evaluated by wound-healing assay under the following conditions: high sodium (HS, 160 mM) and control (CT, 140 mM). Cell viability was assessed by annexin V and propidium iodide labeling. Cyclooxygenase-2 (COX-2) gene expression was analysed by reverse transcription polymerase chain reaction. ERK1/2 phosphorylation was assessed by western blot. Exposure of VSMCs to HS reduced migration, and AT1R blockade prevented this response. HS increased COX-2 gene expression, and COX-2 blockade prevented the reduction in VSMC migration induced by HS. HS also increased ERK1/2 phosphorylation, and ERK1/2 inhibition recovered VSMC migration as well as blocked COX-2 gene expression. The TXA2 receptor blocker, but not the prostacyclin receptor blocker, prevented the HS-induced VSMCs migration decrease. HS reduces the migration of VSMCs by increasing COX-2 gene expression via AT1R-ERK1/2 phosphorylation. In addition, increased COX-2 by HS seems to modulate the reduction of VSMCs migration by the TXA2 receptor.
Asunto(s)
Movimiento Celular/efectos de los fármacos , Músculo Liso Vascular , Miocitos del Músculo Liso/metabolismo , Receptor de Angiotensina Tipo 1/metabolismo , Sodio/farmacología , Animales , Células Cultivadas , Ciclooxigenasa 2/metabolismo , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Músculo Liso Vascular/citología , Músculo Liso Vascular/metabolismo , Miocitos del Músculo Liso/citología , Receptores de Tromboxano A2 y Prostaglandina H2/metabolismo , Sodio/químicaRESUMEN
BACKGROUND: Myocardial infarction (MI) is accompanied by cardiac growth, increased collagen deposition, cell death and new vascularization of the cardiac tissue, which results in reduced ventricular compliance. The MiRNA-29 family (29a, 29b, and 29c) targets mRNAs that encode collagens and other proteins involved in fibrosis. In this study we assessed the effects of swimming training (ST) on expression of the cardiac miRNA-29 family and on genes encoding collagen after MI in rats. METHODS: ST consisted of 60 min/day/10 weeks and began four weeks after MI. MiRNA and collagen expression analysis were performed in the infarcted region (IR), border region (BR) of the infarcted region and in the remote myocardium (RM) of the left ventricle. RESULTS: MiRNA-29a expression increased 32% in BR and 52% in RM in the TR-INF compared with SED-INF. MiRNA-29c increased by 63% in BR and 55% in RM in TR-INF compared with SED-INF group. COL IAI and COL IIIAI decreased by 63% and 62% in TR-INF, respectively, compared with SED-INF. COLIIIAI expression decreased by 16% in TR-INF compared with SED-INF. CONCLUSION: Altogether, our results showed that ST restores cardiac miRNA-29 (a and c) levels and prevents COL IAI and COL IIIAI expression in BR and RM, which may contribute to the improvement in ventricular function induced by swimming training, after MI. © 2014 S. Karger AG, Basel.