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 (...
| Main Authors: | , , , |
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| Format: | Conference or Workshop Item |
| Language: | English |
| Published: |
2015
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| Subjects: | |
| Online Access: | http://irep.iium.edu.my/55255/ http://irep.iium.edu.my/55255/25/55255.pdf |
| Summary: | 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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