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Unacylated Ghrelin Improves Vascular Dysfunction and Attenuates Atherosclerosis during High-Fat Diet Consumption in Rodents

Department of Medical Sciences, University of Trieste, 34127 Trieste, Italy
Department of Translational Medicine, University of Piemonte Orientale “Amedeo Avogadro”, via Solaroli 17, 28100 Novara, Italy
Medical School, Università Vita-Salute San Raffaele, via Olgettina 58, 20132 Milano, Italy
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(3), 499;
Received: 21 December 2018 / Revised: 10 January 2019 / Accepted: 15 January 2019 / Published: 24 January 2019
(This article belongs to the Special Issue Endothelial Dysfunction: Pathophysiology and Molecular Mechanisms)
Unacylated ghrelin (UnGhr) exerts several beneficial actions on vascular function. The aim of this study was to assess the effects of UnGhr on high-fat induced endothelial dysfunction and its underlying mechanisms. Thoracic aortas from transgenic mice, which were overexpressing UnGhr and being control fed either a standard control diet (CD) or a high-fat diet (HFD) for 16 weeks, were harvested and used for the assessment of vascular reactivity, endothelial nitric oxide synthase (eNOS) expression and activity, thiobarbituric acid reactive substances (TBARS) and glutathione levels, and aortic lipid accumulation by Oil Red O staining. Relaxations due to acetylcholine and to DEA-NONOate were reduced (p < 0.05) in the HFD control aortas compared to vessels from the CD animals. Overexpression of UnGhr prevented HFD-induced vascular dysfunction, while eNOS expression and activity were similar in all vessels. HFD-induced vascular oxidative stress was demonstrated by increased (p < 0.05) aortic TBARS and glutathione in wild type (Wt) mice; however, this was not seen in UnGhr mice. Moreover, increased (p < 0.05) HFD-induced lipid accumulation in vessels from Wt mice was prevented by UnGhr overexpression. In conclusion, chronic UnGhr overexpression results in improved vascular function and reduced plaque formation through decreased vascular oxidative stress, without affecting the eNOS pathway. This research may provide new insight into the mechanisms underlying the beneficial effects of UnGhr on the vascular dysfunction associated with obesity and the metabolic syndrome. View Full-Text
Keywords: endothelial dysfunction; obesity; ghrelin; nitric oxide; superoxide endothelial dysfunction; obesity; ghrelin; nitric oxide; superoxide
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Zanetti, M.; Gortan Cappellari, G.; Graziani, A.; Barazzoni, R. Unacylated Ghrelin Improves Vascular Dysfunction and Attenuates Atherosclerosis during High-Fat Diet Consumption in Rodents. Int. J. Mol. Sci. 2019, 20, 499.

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