The effect of perivascular adipose tissue (PVAT) and glucose on contractile properties of rat thoracic and abdominal aortas

Abstract

This thesis, titled 'The effect of perivascular adipose tissue (PVAT) and glucose on contractile properties of rat thoracic and abdominal aortas' was submitted by the author, Hayder Abdulmohsin Al-Siraj to the of Faculty of Biology, Medicine and Health /University of Manchester for the degree of Master of Philosophy, September 2016. Viewing adipose tissue as an inert reservoir for storing energy is no longer valid. The adipose tissue is now recognised as a vital organ with both endocrine and paracrine functions. Owing to its proximity and the lack of facial barrier, the perivascular adipose tissue (PVAT) that surrounds most systemic blood vessels received invaluable recognition as the vessels' fourth layer and a key player in the regulation of the vascular tone. Since the first report by Soltis and Cassis (1991) about the anticontractile effect of PVAT in thoracic aortas contracted to norepinephrine in vitro, a substantial amount of evidence confirmed the inhibitory effect of PVAT and reproduced it against various spasmogens in arteries taken from both animals and humans. Likewise, an increasing number of studies are also reporting a contraction-augmenting effect for the PVAT. In contrary to the early work of Soltis and Cassis (1991), most research groups that followed used physiological saline solutions (PSS) that contained higher glucose concentration (11 mM). Additionally, and in comparison with thoracic aorta, there is a paucity in the number of studies addressing the effect of PVAT in the abdominal segment of the aorta. Therefore, the aim of this project was to study the vasocontractile roles of PVAT in thoracic and abdominal aortas acutely exposed to normal and high glucose contained PSS (5.5 and 11mM, respectively). Using young male Sprague-Dawley rats, isometric contraction and relaxation experiments were performed in isolated thoracic and abdominal aortas with and without PVAT mounted on wire-myography. Results in this study demonstrated a regional difference between thoracic and abdominal aortas in response to 60 mM K+-enriched PSS and relaxation response to acetylcholine. Under normal glucose conditions, brown PVAT was demonstrated to attenuate 60 mM K+- and norepinephrine-induced contractions, while beige PVAT attenuated norepinephrine-induced contractions only. Endothelium denudation abolished the anticontractile effect of brown PVAT against K+ but not against norepinephrine. The incubation of rat aortas in high glucose PSS was demonstrated to enhance the anticontractile effect of PVAT against K+ and phenylephrine. However, endothelium removal was found to abolish the anticontractile effect of PVAT against K+- and phenylephrine-induced contractions. PVAT-transfer experiments demonstrated that the effect of PVAT is not transferable in thoracic and abdominal aortas contracted to norepinephrine and phenylephrine, respectively. Furthermore, the acute exposure of PVAT-cleaned, thoracic and abdominal aortas to high glucose PSS was demonstrated to augment the reactivity of phenylephrine-induced contractions, an effect that was found to be endothelium- and/or glucose-dependent in rat aortas. Additionally, the increased O-GlcNAcylation posttranslational modification of vascular proteins is speculated to mediate, at least in part, the augmented reactivity of PVAT-cleaned, thoracic and abdominal aortas to phenylephrine under conditions of hyperglycaemia. Lastly but not least, brown PVAT was demonstrated to severely impair the endothelium-dependent relaxation response to acetylcholine, suggesting an additional procontractile role for brown PVAT in the thoracic aorta.

Date of Award	1 Aug 2017
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Alison Gurney (Supervisor) & Gillian Edwards (Supervisor)