Abstract
BackgroundHyperglycemia-induced endothelial hyperpermeability is crucial to cardiovascular disorders and macro-vascular complications in diabetes mellitus. The objective of this study is to investigate the effects of green tea polyphenols (GTPs) on endothelial hyperpermeability and the role of nicotinamide adenine dinucleotide phosphate (NADPH) pathway.MethodsMale Wistar rats fed on a high fat diet (HF) were treated with GTPs (0, 0.8, 1.6, 3.2 g/L in drinking water) for 26 weeks. Bovine aortic endothelial cells (BAECs) were treated with high glucose (HG, 33 mmol/L) and GTPs (0.0, 0.4, or 4 μg/mL) for 24 hours in vitro. The endothelial permeabilities in rat aorta and monolayer BAECs were measured by Evans blue injection method and efflux of fluorescein isothiocyanate (FITC)-dextran, respectively. The reactive oxygen species (ROS) levels in rat aorta and monolayer BAECs were measured by dihydroethidium (DHE) and 2′, 7′-dichloro-fluorescein diacetate (DCFH-DA) fluorescent probe, respectively. Protein levels of NADPH oxidase subunits were determined by Western-blot.ResultsHF diet-fed increased the endothelial permeability and ROS levels in rat aorta while HG treatments increased the endothelial permeability and ROS levels in cultured BAECs. Co-treatment with GTPs alleviated those changes both in vivo and in vitro. In in vitro studies, GTPs treatments protected against the HG-induced over-expressions of p22phox and p67phox. Diphenylene iodonium chloride (DPI), an inhibitor of NADPH oxidase, alleviated the hyperpermeability induced by HG.ConclusionsGTPs could alleviate endothelial hyperpermeabilities in HF diet-fed rat aorta and in HG treated BAECs. The decrease of ROS production resulting from down-regulation of NADPH oxidase contributed to the alleviation of endothelial hyperpermeability.
Highlights
Hyperglycemia-induced endothelial hyperpermeability is crucial to cardiovascular disorders and macro-vascular complications in diabetes mellitus
We investigated the effects of green tea polyphenols (GTPs) on the endothelial permeability in aortas of rats fed on a high fat diet (HF) diet and in cultured Bovine aortic endothelial cells (BAECs) exposed to HG, and the involvements of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase as well
GTPs reduced reactive oxygen species (ROS) production induced by HF in rat aorta and by HG in BAECs As shown in Figure 2A and B, Additional file 2, HF treatment significantly increased the ROS level of rat aortas compared to the control group
Summary
Hyperglycemia-induced endothelial hyperpermeability is crucial to cardiovascular disorders and macro-vascular complications in diabetes mellitus. The precise mechanism that leads to cardiovascular disease is not fully understood, endothelial dysfunction plays a vital role [2]. ROS induction is mainly attributable to the production of superoxide anion (O2 ·−) catalyzed by NADPH oxidase [7,9]. The variability of p22phox, which is crucial for superoxide anion production in vascular cells [13], is a cause of variation in ROS production in human [14]. Alleviation of NADPH oxidase activation by regulation of NADPH subunit expressions is highly likely to efficiently ameliorate endothelial ROS production and play a role in alleviation of the hyperpermeability induced by hyperlipidemia/hyperglycemia
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