Etanercept Prevents Endothelial Dysfunction in Cafeteria Diet-Fed Rats.

Scăunaşu Răzvan-Valentin,Nihat Zafer Utkan,Gulcin Gacar,Popescu Bogdan,Sertaç Ata Güler,Selenay Furat Rencber,Tijen Utkan,Lupușoru Mircea,Bălălău Cristian,Yusufhan Yazir,Tuğçe Demirtaş Şahin

doi:10.3390/ijerph19042138

Abstract

: BackgroundObesity is associated with endothelial dysfunction and this relationship is probably mediated in part by inflammation. Objective: The current study evaluated the effects of etanercept, a tumor necrosis factor-alpha (TNF-α) inhibitor, on endothelial and vascular reactivity, endothelial nitric oxide synthase (eNOS) immunoreactivity, and serum and aortic concentrations of TNF-α in a diet-induced rat model. Design and results: Male weanling Wistar rats were exposed to a standard diet and cafeteria diet (CD) for 12 weeks and etanercept was administered during CD treatment. Isolated aortas of the rats were used for isometric tension recording. Carbachol-induced relaxant responses were impaired in CD-fed rats, while etanercept treatment improved these endothelium-dependent relaxations. No significant change was observed in papaverine- and sodium nitroprusside (SNP)-induced relaxant responses. eNOS expression decreased in CD-fed rats, but no change was observed between etanercept-treated CD-fed rats and control rats. CD significantly increased both the serum and the aortic levels of TNF-α, while etanercept treatment suppressed these elevated levels. CD resulted in a significant increase in the body weight of the rats. Etanercept-treated (ETA) CD-fed rats gained less weight than both CD-fed and control rats.

Highlights

Introduction iationsObesity is a worldwide health problem associated with cardiovascular diseases, type2 diabetes, chronic inflammation, and cancer [1]
At the end of the experimental period, the cafeteria diet induced a significant increase in body weight (CD group) compared with the standard diet (Figure 1, Table 1)
One group demonstrated that Ach-induced Nitric oxide (NO) production and endothelial nitric oxide synthase (eNOS) expression in isolated coronary arteries from obese Zucker rats markedly decreased compared with the lean control rats, via the elevated levels of circulating and protein expression of TNF-α [37]. In line with these data, we showed that TNF-α blockade with chronic etanercept treatment prevented obesity-induced endothelial dysfunction by increasing thoracic aortic eNOS expression and decreased serum concentrations of TNF-α in CD-fed rat, indicating the role of TNF-α in endothelial dysfunction related with obesity, and the close relationship between obesity and inflammation

Summary

Introduction

Obesity is a worldwide health problem associated with cardiovascular diseases, type. 2 diabetes, chronic inflammation, and cancer [1]. It is characterized by detrimental effects on vasculature including reduced endothelial function in different vascular beds [2,3,4]. Endothelial dysfunction, an independent predictor for the initiation and progression of atherosclerosis, has been established as a key mediator that links obesity with cardiovascular diseases [5]. The vascular endothelium plays a crucial role in modulating vascular tone and vasomotor function and is involved in the regulation of inflammation, platelet aggregation, and thrombosis. Nitric oxide (NO) is the major mediator of these functions and physiological processes [6]. Endothelial dysfunction is generally associated with reduced NO bioavailability [7]. It has been demonstrated that vascular inflammation secondary to elevated

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