eprintid: 1457386
rev_number: 39
eprint_status: archive
userid: 608
dir: disk0/01/45/73/86
datestamp: 2015-02-05 08:52:42
lastmod: 2019-10-19 07:42:29
status_changed: 2015-02-05 08:52:42
type: thesis
metadata_visibility: show
item_issues_count: 0
creators_name: Shen, L
title: Vascular function in abdominal adipose tissue: vascular tone, angiogenic and secretory capacity
ispublished: unpub
divisions: A01
divisions: B02
divisions: D14
divisions: GA2
keywords: adipose tissue, type 2 diabetes, noradrenaline, vasculature, tissue fibrosis, angiogenesis
abstract: Background Adipose tissue (AT) growth is critically dependant on the functional vascular support. Optimal angiogenesis and functional vascular tone ensure the sufficient supply of oxygen, insulin, and nutrients, thus preventing AT hypoxia and insulin resistance. Meanwhile, vascular function is regulated by vasoactive molecules released from AT. Abdominal AT expansion including subcutaneous and omental depots (SAT and OAT respectively) contributes to increased risks of cardiovascular vascular disease. This thesis investigated: 1. The depot- and diabetes-specific difference in noradrenaline synthesis and noradrenaline-mediated vasoconstriction and tissue fibrosis; 2. The depot- and diabetes-specific differences of angiogenesis and angiogenesis-related mRNA and protein expression; 3. The adipokine secretion from perivascular adipose tissue (PVAT) and vessels. Methods Abdominal SAT and OAT from morbid obese patients were used for 1) cell and tissue culture; 2) histochemistry and immunohistochemistry; 3) myography; 4) real-time PCR and western blot; 5) ELISAs. Results Study 1: In non-diabetic group, SAT showed significantly higher sensitivity to noradrenaline (NA)-induced vasoconstriction compared to OAT and diabetic group, which was concomitant with lower local NE synthesis and collagen deposition. Study 2: SAT of non-diabetic subjects had lower capillary density, angiogenic capacity, and downregulation of angiogenesis-related genes compared with OAT and diabetics. Study 3: In PVAT study, for the first time, we discovered adiponectin expression from human endothelial cells (ECs). Conclusion Study 1: SAT in non-diabetic obese patients was protected by its preserved NA sensitivity, functional vasoreactivity and low levels of tissue fibrosis, while elevated, local, chronic NA levels may desensitise the vessels of OAT and diabetics, and lead to elevated collagen deposition. Study 2: High levels of angiogenesis in OAT and diabetes did not reverse local hypoxia, which may be due to its compromised vascular function. Study 3: Moreover, endothelium-derived adiponectin may be important protecting endothelial function in cardiovascular events.
date: 2014-12-28
vfaculties: VGHCSCI
oa_status: green
full_text_type: other
thesis_class: doctoral_open
language: eng
thesis_view: UCL_Thesis
primo: open
primo_central: open_green
verified: verified_manual
elements_source: Manually entered
elements_id: 996826
lyricists_name: Shen, Lei
lyricists_id: SLEIX47
full_text_status: public
pagerange: ? - ?
pages: 183
institution: UCL (University College London)
department: Division of Medicine
thesis_type: Doctoral
citation:        Shen, L;      (2014)    Vascular function in abdominal adipose tissue: vascular tone, angiogenic and secretory capacity.                   Doctoral thesis , UCL (University College London).     Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/1457386/2/Final%20Thesis%20final%20correction.pdf