Signalling pathways controlling glycosaminoglycan (GAG) chain synthesizing enzyme gene expression as potential therapeutic target for atherosclerosis

Heart disease is the leading cause of death in Australia. Atherosclerosis is the major the underlying cause of most heart disease. It is a pathological condition where accumulation of LDL cholesterol and inflammatory products in the blood vessel wall leads to formation of atherosclerotic plaques. Tr...

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Main Author:	Rostam, Muhamad Ashraf
Format:	Conference or Workshop Item
Language:	English
Published:	2014
Subjects:	R Medicine (General) RM Therapeutics. Pharmacology
Online Access:	http://irep.iium.edu.my/55389/ http://irep.iium.edu.my/55389/19/55389.pdf

id	iium-55389
recordtype	eprints
spelling	iium-553892017-04-25T02:52:28Z http://irep.iium.edu.my/55389/ Signalling pathways controlling glycosaminoglycan (GAG) chain synthesizing enzyme gene expression as potential therapeutic target for atherosclerosis Rostam, Muhamad Ashraf R Medicine (General) RM Therapeutics. Pharmacology Heart disease is the leading cause of death in Australia. Atherosclerosis is the major the underlying cause of most heart disease. It is a pathological condition where accumulation of LDL cholesterol and inflammatory products in the blood vessel wall leads to formation of atherosclerotic plaques. Treatments to reduce atherosclerosis have mainly focused on reducing established risk factors like high cholesterol level. However, the efficacy of such treatments is limited to around 30 percent. New targets directed at the blood vessel wall are important areas that are being investigated. This includes focusing on the role of extracellular matrix components like proteoglycans that trap LDL. TGF-β is a growth factor associated with atherosclerosis. In vascular smooth muscle cells, TGF-β induces increased elongation of the sugar chain known as glycosaminoglycan (GAG) on proteoglycans and hence increases its size. This leads to increased binding to LDL in the initial stage of atherosclerosis. Our hypothesis is that the increase in elongation of GAG chain is regulated by the TGF-β mediated increase in expression of enzymes that synthesize this chain. However, the specific enzymes and the precise signalling pathways that lead to this up-regulation are not known. Therefore, we aim to describe the TGF-β signalling pathway and the intermediary protein kinases and Smad transcription factors that lead to GAG gene expression. This study uses pharmacological as well as molecular approaches to understand the critical kinases and protein components that are involved. The outcome of this study is important because the key elements we identify will provide new information about the signalling pathways regulating modification of proteoglycan synthesis. This will facilitate the identification of therapeutic targets in prevention of atherosclerosis. 2014 Conference or Workshop Item NonPeerReviewed application/pdf en http://irep.iium.edu.my/55389/19/55389.pdf Rostam, Muhamad Ashraf (2014) Signalling pathways controlling glycosaminoglycan (GAG) chain synthesizing enzyme gene expression as potential therapeutic target for atherosclerosis. In: The Higher Degree by Research Student Conference 2014, Melbourne, Australia. (Unpublished)
repository_type	Digital Repository
institution_category	Local University
institution	International Islamic University Malaysia
building	IIUM Repository
collection	Online Access
language	English
topic	R Medicine (General) RM Therapeutics. Pharmacology
spellingShingle	R Medicine (General) RM Therapeutics. Pharmacology Rostam, Muhamad Ashraf Signalling pathways controlling glycosaminoglycan (GAG) chain synthesizing enzyme gene expression as potential therapeutic target for atherosclerosis
description	Heart disease is the leading cause of death in Australia. Atherosclerosis is the major the underlying cause of most heart disease. It is a pathological condition where accumulation of LDL cholesterol and inflammatory products in the blood vessel wall leads to formation of atherosclerotic plaques. Treatments to reduce atherosclerosis have mainly focused on reducing established risk factors like high cholesterol level. However, the efficacy of such treatments is limited to around 30 percent. New targets directed at the blood vessel wall are important areas that are being investigated. This includes focusing on the role of extracellular matrix components like proteoglycans that trap LDL. TGF-β is a growth factor associated with atherosclerosis. In vascular smooth muscle cells, TGF-β induces increased elongation of the sugar chain known as glycosaminoglycan (GAG) on proteoglycans and hence increases its size. This leads to increased binding to LDL in the initial stage of atherosclerosis. Our hypothesis is that the increase in elongation of GAG chain is regulated by the TGF-β mediated increase in expression of enzymes that synthesize this chain. However, the specific enzymes and the precise signalling pathways that lead to this up-regulation are not known. Therefore, we aim to describe the TGF-β signalling pathway and the intermediary protein kinases and Smad transcription factors that lead to GAG gene expression. This study uses pharmacological as well as molecular approaches to understand the critical kinases and protein components that are involved. The outcome of this study is important because the key elements we identify will provide new information about the signalling pathways regulating modification of proteoglycan synthesis. This will facilitate the identification of therapeutic targets in prevention of atherosclerosis.
format	Conference or Workshop Item
author	Rostam, Muhamad Ashraf
author_facet	Rostam, Muhamad Ashraf
author_sort	Rostam, Muhamad Ashraf
title	Signalling pathways controlling glycosaminoglycan (GAG) chain synthesizing enzyme gene expression as potential therapeutic target for atherosclerosis
title_short	Signalling pathways controlling glycosaminoglycan (GAG) chain synthesizing enzyme gene expression as potential therapeutic target for atherosclerosis
title_full	Signalling pathways controlling glycosaminoglycan (GAG) chain synthesizing enzyme gene expression as potential therapeutic target for atherosclerosis
title_fullStr	Signalling pathways controlling glycosaminoglycan (GAG) chain synthesizing enzyme gene expression as potential therapeutic target for atherosclerosis
title_full_unstemmed	Signalling pathways controlling glycosaminoglycan (GAG) chain synthesizing enzyme gene expression as potential therapeutic target for atherosclerosis
title_sort	signalling pathways controlling glycosaminoglycan (gag) chain synthesizing enzyme gene expression as potential therapeutic target for atherosclerosis
publishDate	2014
url	http://irep.iium.edu.my/55389/ http://irep.iium.edu.my/55389/19/55389.pdf
first_indexed	2023-09-18T21:18:16Z
last_indexed	2023-09-18T21:18:16Z
_version_	1777411709319774208

Signalling pathways controlling glycosaminoglycan (GAG) chain synthesizing enzyme gene expression as potential therapeutic target for atherosclerosis

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