RESUMO
INTRODUCTION: Obesity alters several metabolic activities, subsequently leading to the development of cardiovascular diseases. The insulin resistance-induced obesity stimulates vasodilatation and vasoconstriction imbalance, which ends up in cardiac vascular remodeling. Therefore, we aimed to investigate the effect of obesity in cardiac diseases with a focus on inflammatory mediators associated with endothelial dysfunction. MATERIALS AND METHODS: Rats (3 months old, weighing 200 g) were divided into control (n=6) and the obese groups, which included rats fed on a high-fat diet (HFD, n=6 in each subgroup) for 1 month (OB1), 2 months (OB2), and 4 months (OB4). Then, the rats were sacrificed, and their hearts were harvested for histological quantification as well as the quantification of the mRNA expression of inflammatory mediators, eNOS, and ppET-1 by reverse transcriptasepolymerase chain reaction (RT-PCR). Sirius Red staining was performed to assess vascular remodeling, while immunohistochemistry of CD68 was performed to assess the localization of macrophage. RESULTS: HFD-induced obesity was significantly manifested in the obese groups relative to that in the control group. It was followed by an increase in the mRNA expression of inflammatory mediators in the obese groups when compared to that in the control group. Long-term obesity promoted vascular remodeling, which was noted in the OB4 group, along with downregulation of the eNOS mRNA expression and the upregulation of the ppET-1 mRNA expression. CONCLUSION: Obesity associated with inflammation and vascular remodeling in the heart.
Assuntos
Obesidade , Remodelação Vascular , Animais , Inflamação/metabolismo , Inflamação/patologia , Mediadores da Inflamação , Obesidade/complicações , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RatosRESUMO
INTRODUCTION: Diabetes mellitus (DM) leads to microvascular injury development and produces diabetes nephropathy (DN) with proteinuria, tubular injury, apoptosis and autophagy with upregulation of Bax, BASP and mTORC-1. Megalin, Cubilin and Neutrophil Gelatinase Associated Lipocalin (NGAL) play role in acute pathological condition of kidney injury, however its expression in chronic and slowly progressive kidney injury such as DN has not been elucidated yet. This study focuses upregulation of Megalin, Cubilin and NGAL in association with tubular injury and apoptosis in DN condition. MATERIALS AND METHODS: Diabetic condition was performed with intraperitoneal injection of Streptozotocin 60 mg/kg body weight (BW) in Sprague Dawley rats (2 months old, n=24), and were kept for 1, 2, and 4 months (DM1, DM2, and DM4, respectively). Control group was injected with NaCl 0.9%. Serum glucose level and proteinuria score were assessed, furthermore tubular injury score was quantified based on Periodic-Acid Schiff (PAS) staining. Reverse Transcriptase-PCR (RT-PCR) was carried out for NGAL, Megalin, Cubilin, m-TOR, Bax, and BASP-1 mRNA expression. Data were analyzed using SPSS 22 software. RESULTS: DM led to kidney injury in this model with significant higher glucose level, proteinuria and tubular injury, especially in DM4 group which represented chronic phase of DN and CKD. These findings associated with upregulation of Megalin,Cubilin and NGAL mRNA expression in DM groups, especially in DM4 group. DM4 group also revealed higher expression of Bax, BASP and mTOR mRNA expression which demonstrated apoptosis. CONCLUSION: Megalin, Cubilin and NGAL upregulation may represent tubular injury and apoptosis as progression of DN.
Assuntos
Injúria Renal Aguda , Diabetes Mellitus , Injúria Renal Aguda/genética , Animais , Apoptose , Humanos , Rim , Lipocalina-2/genética , Proteína-2 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , Proteína-2 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo , RNA Mensageiro/genética , Ratos , Ratos Sprague-Dawley , Receptores de Superfície Celular , Regulação para CimaRESUMO
We examined the upregulation of ET-1/ETBR/eNOS signaling in renoprotective effect of vitamin D in kidney fibrosis model in mice using unilateral ureteral obstruction (UUO). One group was treated with intraperitoneal injection of 0.125 mg/kg of Calcitriol (UUO+VD). Vascular remodeling was quantified based on lumen area and lumen/wall area ratio (LWAR) of intrarenal arteries using Sirius Red staining. ET-1, ETBR, eNOS, CD31 and VEGF mRNA expressions were quantified using qRT-PCR. Focusing on endothelin-1 (ET-1) signaling in endothelial cells (EC), siRNA of ET-1 was performed in human umbilical vein endothelial cells (HUVEC) for reducing ET-1 expression. Then HUVECs were treated with and without 100 nM Calcitriol treatment in hypoxic and normoxic conditions to elucidate ET-1/eNOS signaling. Our in vivo study revealed vascular remodeling and renal ischemia attenuation after Calcitriol treatment. Vascular remodeling was attenuated in the UUO+VD group as shown by increasing lumen areas and LWAR in intrarenal arteries. These findings were associated with significant higher CD31 and VEGF mRNA expression compared to the UUO group. Vitamin D treatment also increased ET-1, ETBR and eNOS mRNA expressions. Our in vitro study demonstrated Calcitriol induced ET-1 and eNOS mRNA expressions upregulation in HUVEC under normoxic and hypoxic condition. Meanwhile, siRNA for ET-1 inhibited the upregulation of eNOS mRNA expression after Calcitriol treatment. Vitamin D ameliorates kidney fibrosis through attenuating vascular remodeling and ischemia with upregulating ET-1/ETBR and eNOS expression.
