Mechanical stretch enhances the expression of resistin gene in cultured cardiomyocytes via tumor necrosis factor-α

Abstract

The heart is a resistin target tissue and can function as an autocrine organ. We sought to investigate whether cyclic mechanical stretch could induce resistin expression in cardiomyocytes and to test whether there is a link between the stretch-induced TNF-alpha and resistin. Neonatal Wistar rat cardiomyocytes grown on a flexible membrane base were stretched by vacuum to 20% of maximum elongation at 60 cycles/min. Cyclic stretch significantly increased resistin protein and mRNA expression after 2-18 h of stretch. Addition of PD-98059, TNF-alpha antibody, TNF-alpha receptor antibody, and ERK MAP kinase small interfering RNA 30 min before stretch inhibited the induction of resistin protein. Cyclic stretch increased, whereas PD-98059 abolished, the phosphorylated ERK protein. Gel-shift assay showed a significant increase in DNA-protein binding activity of NF-kappaB after stretch, and PD-98059 abolished the DNA-protein binding activity induced by cyclic stretch. DNA binding complexes induced by cyclic stretch could be supershifted by p65 monoclonal antibody. Cyclic stretch increased resistin promoter activity, whereas PD-98059 and p65 antibody decreased resistin promoter activity. Cyclic stretch significantly increased TNF-alpha secretion from myocytes. Recombinant resistin protein and conditioned medium from stretched cardiomyocytes reduced glucose uptake in cardiomyocytes, and recombinant small interfering RNA of resistin or TNF-alpha antibody reversed glucose uptake. In conclusion, cyclic mechanical stretch enhances resistin expression in cultured rat neonatal cardiomyocytes. The stretch-induced resistin is mediated by TNF-alpha, at least in part, through ERK MAP kinase and NF-kappaB pathways. Glucose uptake in cardiomyocytes was reduced by resistin upregulation.

Resistin and Cardiac Remodeling in Patients with Obstructive Sleep Apnea

“…The haemodynamic burden, evaluated by the NT-pro-BNP showed no significant decrease of plasma NT-pro-BNP in the bilevel positive airway pressure group. Despite that recent experimental data [43], determine mechanical stretch as an enhancer of of resistin expression, the results of our can not confirm this.…”

Sitagliptin decreases ventricular arrhythmias by attenuated glucose-dependent insulinotropic polypeptide (GIP)-dependent resistin signalling in infarcted rats

“…In addition, although resistin mRNA expression levels have been reported to be the highest in white adipose tissue in rodents, resistin has also been found to be expressed in the heart [8]. Resistin has also been shown to impair glucose transport in isolated cardiomyocytes [9] and to be upregulated by cyclic stretch and aorta-caval shunt [10], suggesting that resistin mRNA is expressed in cardiomyocytes.…”

Role of resistin in cardiac contractility and hypertrophy

“…TZD treatment resulted in decreased plasma resistin levels in patients with type 2 diabetes [10], suggesting resistin plays an important role in the etiology of insulin resistance and diabetes; however, others have failed to show this association [11], [12]. Recently, resistin was shown to impair glucose transport in isolated cardiomyocytes [13] and to be up-regulated by cyclic stretch and aorta-caval shut [14], suggesting resistin may affect cardiac function in animal models. However, the underlying mechanism by which resistin impairs cardiac function is unknown.…”