Cyclin dependent Kinases as potential therapeutic targets for atherosclerosis

Cardiovascular disease is the leading cause of death among adults worldwide and atherosclerosis is the major underlying pathology. The pre-inflammatory stage of atherosclerosis is associated with proteoglycan glycosaminoglycan (GAG) chain hyper-elongation that results in increased proteoglycan (...

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Main Authors: Rostam, Muhamad Ashraf, Piva, Terence J., Osman, Narin, Little, Peter J.
Format: Proceeding Paper
Language:English
Published: 2015
Subjects:
Online Access:http://irep.iium.edu.my/55255/
http://irep.iium.edu.my/55255/25/55255.pdf
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author Rostam, Muhamad Ashraf
Piva, Terence J.
Osman, Narin
Little, Peter J.
author_facet Rostam, Muhamad Ashraf
Piva, Terence J.
Osman, Narin
Little, Peter J.
author_sort Rostam, Muhamad Ashraf
building IIUM Repository
collection Online Access
description Cardiovascular disease is the leading cause of death among adults worldwide and atherosclerosis is the major underlying pathology. The pre-inflammatory stage of atherosclerosis is associated with proteoglycan glycosaminoglycan (GAG) chain hyper-elongation that results in increased proteoglycan (PG) binding to low density lipoprotein (LDL). Elevated GAG synthesizing enzyme mRNA expression has been shown to be linked to in vivo atherosclerosis development. Transforming Growth Factor-β (TGF-β) is associated with atherosclerosis and mediates GAG chain hyper-elongation. The specific GAG synthesizing enzymes and the signalling pathways are unclear. TGF-β signals through phosphorylation of Smad 2/3 at its C-terminus and it can also lead to other serine/threonine kinases, including ERK, to phosphorylate Smad2 in the linker region. This leads to TGF-β mediated PG hyper-elongation in human vascular smooth muscle cells (VSMC). Little is known regarding the involvement of CDK in TGF-β mediated PG synthesis in human VSMC. Understanding this signalling pathway facilitates the identification of a therapeutic target to prevent atheroslcerosis
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spelling iium-552552017-04-20T01:53:55Z http://irep.iium.edu.my/55255/ Cyclin dependent Kinases as potential therapeutic targets for atherosclerosis Rostam, Muhamad Ashraf Piva, Terence J. Osman, Narin Little, Peter J. RM Therapeutics. Pharmacology Cardiovascular disease is the leading cause of death among adults worldwide and atherosclerosis is the major underlying pathology. The pre-inflammatory stage of atherosclerosis is associated with proteoglycan glycosaminoglycan (GAG) chain hyper-elongation that results in increased proteoglycan (PG) binding to low density lipoprotein (LDL). Elevated GAG synthesizing enzyme mRNA expression has been shown to be linked to in vivo atherosclerosis development. Transforming Growth Factor-β (TGF-β) is associated with atherosclerosis and mediates GAG chain hyper-elongation. The specific GAG synthesizing enzymes and the signalling pathways are unclear. TGF-β signals through phosphorylation of Smad 2/3 at its C-terminus and it can also lead to other serine/threonine kinases, including ERK, to phosphorylate Smad2 in the linker region. This leads to TGF-β mediated PG hyper-elongation in human vascular smooth muscle cells (VSMC). Little is known regarding the involvement of CDK in TGF-β mediated PG synthesis in human VSMC. Understanding this signalling pathway facilitates the identification of a therapeutic target to prevent atheroslcerosis 2015 Proceeding Paper NonPeerReviewed application/pdf en http://irep.iium.edu.my/55255/25/55255.pdf Rostam, Muhamad Ashraf and Piva, Terence J. and Osman, Narin and Little, Peter J. (2015) Cyclin dependent Kinases as potential therapeutic targets for atherosclerosis. In: 78th Harden Conference: Protein Kinases in Health and Disease, 15th—18th September 2015, Winchester, United Kingdom. (Unpublished)
spellingShingle RM Therapeutics. Pharmacology
Rostam, Muhamad Ashraf
Piva, Terence J.
Osman, Narin
Little, Peter J.
Cyclin dependent Kinases as potential therapeutic targets for atherosclerosis
title Cyclin dependent Kinases as potential therapeutic targets for atherosclerosis
title_full Cyclin dependent Kinases as potential therapeutic targets for atherosclerosis
title_fullStr Cyclin dependent Kinases as potential therapeutic targets for atherosclerosis
title_full_unstemmed Cyclin dependent Kinases as potential therapeutic targets for atherosclerosis
title_short Cyclin dependent Kinases as potential therapeutic targets for atherosclerosis
title_sort cyclin dependent kinases as potential therapeutic targets for atherosclerosis
topic RM Therapeutics. Pharmacology
url http://irep.iium.edu.my/55255/
http://irep.iium.edu.my/55255/25/55255.pdf