Shen, L; (2014) Vascular function in abdominal adipose tissue: vascular tone, angiogenic and secretory capacity. Doctoral thesis , UCL (University College London).

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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.

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