WNT pathway regulation of lipid handling and inflammation in organ function: the role of LRP5

[eng] INTRODUCTION: cardiovascular diseases are the first cause of premature mortality worldwide. Atherosclerosis is the most common underlying cause of cardiovascular disease. This is a complex condition triggered by the accumulation of modified cholesterol in the vascular wall, which induces infla...

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Detalhes bibliográficos
Autor: Luquero Gomez, Aureli
Tipo de documento: tese
Estado:Versão publicada
Data de publicação:2024
País:España
Recursos:Universidad de Barcelona
Repositório:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/218599
Acesso em linha:https://hdl.handle.net/2445/218599
http://hdl.handle.net/10803/693605
Access Level:Acceso aberto
Palavra-chave:Genètica mèdica
Colesterol
Malalties cardiovasculars
Aterosclerosi
Inflamació
Medical genetics
Cholesterol
Cardiovascular diseases
Atherosclerosis
Inflammation
Descrição
Resumo:[eng] INTRODUCTION: cardiovascular diseases are the first cause of premature mortality worldwide. Atherosclerosis is the most common underlying cause of cardiovascular disease. This is a complex condition triggered by the accumulation of modified cholesterol in the vascular wall, which induces inflammatory and fibrotic processes. Hypercholesterolemia is the elevation of circulating cholesterol levels in blood, which affects cholesterol homeostasis in different tissues and organs. Canonical WNT pathway is an evolutionary conserved signalling pathway with a role in embryonic development and cell fate. Low-density Lipoprotein Receptor – related protein 5 (LRP5) is a receptor that triggers the canonical WNT signalling and uptakes circulating low-density lipoproteins (LDL). It is our hypothesis that LRP5 and the canonical WNT signalling play a key role in the cellular response to cholesterol exposure in different tissues. OBJECTIVES: the aim of this thesis is to identify the role of LRP5 in different cell types and tissues modulated by hypercholesterolemia including circulating macrophages and cell lineages of the liver and the adipose tissue. Additionally, this thesis focuses on the study of LRP5 roles during the inflammatory response induced by atherosclerosis and its role in the brain (an organ with a heavily regulated cholesterol homeostasis).