Title:

Angiogenesis in model of metabolic syndrome in mice with deficiency of retinoic acid receptor gene (RXR alfa) in hepatocytes

Author:

Raźny, Urszula

Subject:

adipogenesis ; RXR ; angiogenesis ; metabolic syndrome

Abstract:

The model used in the study – mice with deletion of RXRα gene in hepatocytes (hRXRα ko) made it possible to investigate the effect of metabolic disturbances - higher cholesterol and leptin level in the blood (with normal insulin level and improved glucose tolerance) on angiogenesis.In order to expose metabolic syndrome parameters, hRXRα ko and wild type mice were fed either high fat diet or control, standard diet for 7 weeks. During feeding mice were weighted and biochemical parametres were measured in the blood. To estimate angiogenic response, in 6th week of feeding, animals were subcutaneously injected with matrigel containing bFGF [25nM] for 6 days. Angiogenesis was assumed in matrigel paraffin sections stained immunohistochemically against CD31 antigen. In matrigel plug cells, gene expression was also analysed.High fat diet feeding resulted in higher cholesterol and leptin level in serum and also in the tendency to decreased angiogenic response (number of vessels with lumen) in hRXRα ko mice. Gene expression analysis in matrigel plugs from hRXRα ko mice showed inhibition of genes related to angiogenesis as well as activation of: apoptosis inducers, proinflammatory genes and genes connected with initial steps of adipogenesis. Presented results suggest that angiogenic response in hRXRα ko mice is mainly regulated by disturbances of lipid metabolism, but not by proangiogenic ; leptin. The reason of weaker angiogenic response in these mice could be activation of apoptosis which is caused on the one hand, by lipotoxicity in cells participating in neovascularisation and on the other hand, by adipogenesis induction

Place of publishing:

Kraków

Level of degree:

2 - studia doktoranckie

Degree discipline:

biochemia

Degree grantor:

Wydział Lekarski

Promoter:

Dembińska-Kieć, Aldona

Date:

2012

Date issued:

2011

Type:

Praca doktorska

Call number:

ZB-116986

Language:

pol

Access rights:

nieograniczony

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