Rôle d'autotaxine (ATX) dans le développement du rétrécissement aortique calcifié (RAC)

Authors: Nsaibia, Mohamed Jalloul
Advisor: Mathieu, Patrick
Abstract: Calcific aortic valve disease (CAVD) is the most common valvular disease, which is characterized by a progressive mineralization of aortic valve. So far, there is no effective medical therapy able to stop or slow the natural course of this disease. Surgical aortic valve replacement is the only available treatments of severe symptomatic aortic stenosis. Therefore, identify the key factors as well as molecular processes involved in the pathogenesis of CAVD is crucial to develop efficient pharmaceutical approaches able to prevent or to slow the progression of aortic stenosis. CAVD is a progressive disease characterized by ectopic calcification of the aortic valve leaflets. It has long been considered as a degenerative process of the aortic valve linked to aging. However, a growing number of studies have revealed that this disease is an active process likely related to atherosclerosis. Therefore, CAVD seems to be a complex pathology involving several pathological processes, including lipid retention, oxidation, chronic inflammation, fibrotic remodeling and calcification. In this regard, assessment of the molecular process whereby lipids promote the mineralization of aortic valve is required to understand the pathophysiological mechanisms leading to CAVD. Furthermore, investigations are needed to identify therapeutic targets and to open novel therapeutic avenues for the treatment of CAVD. The general objectives of my PhD project are: (1) To determine the role of ATX in mediating lipid-induced mineralization of valve interstitial cells (VICs); (2) To understand the mechanisms and signaling pathways by which lysophosphatidic acid (LPA) promotes inflammation and the mineralization of the aortic valve; (3) To determine the role of ATX-LPA in a mouse model of CAVD.
Document Type: Thèse de doctorat
Issue Date: 2018
Open Access Date: 9 October 2018
Permalink: http://hdl.handle.net/20.500.11794/31586
Grantor: Université Laval
Collection:Thèses et mémoires

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