Methotrexate inhibits proliferation but not proteoglycan synthesis or glycosaminoglycan hyperelongation in human vascular smooth muscle cells

Objectives: Atherosclerosis is a disease process involving the early deposition of lipids in the vessel wall trapped by modified proteoglycans and subsequently a chronic inflammatory process leading to the clinical events. MTX has been chosen to study the potential efficacy of an anti inflammatory...

Full description

Bibliographic Details
Main Authors:	Little, Peter J., Getachew, Robel, Kamato, Danielle, Rostam, Muhamad Ashraf, Cohen, Neale, Chan, Vincent, Osman, Narin
Format:	Article
Language:	English
Published:	OMICS International 2015
Subjects:	R Medicine (General) RM Therapeutics. Pharmacology
Online Access:	http://irep.iium.edu.my/55384/ http://irep.iium.edu.my/55384/ http://irep.iium.edu.my/55384/ http://irep.iium.edu.my/55384/1/9.%20Little%202015%20methotrexate-.pdf

id	iium-55384
recordtype	eprints
spelling	iium-553842017-04-04T04:49:15Z http://irep.iium.edu.my/55384/ Methotrexate inhibits proliferation but not proteoglycan synthesis or glycosaminoglycan hyperelongation in human vascular smooth muscle cells Little, Peter J. Getachew, Robel Kamato, Danielle Rostam, Muhamad Ashraf Cohen, Neale Chan, Vincent Osman, Narin R Medicine (General) RM Therapeutics. Pharmacology Objectives: Atherosclerosis is a disease process involving the early deposition of lipids in the vessel wall trapped by modified proteoglycans and subsequently a chronic inflammatory process leading to the clinical events. MTX has been chosen to study the potential efficacy of an anti inflammatory agent in preventing atherosclerosis and secondary cardiovascular disease in the cardiovascular inflammation reduction trial (CIRT). Methods: We have investigated cell proliferation and growth factor stimulated proteoglycan synthesis in vascular smooth muscle (VSMC) to assess some of the direct effects of MTX. Experiments were conducted in cultured human VSMC. Proliferation was assessed by the gold standard technique of cell counting and proteoglycan synthesis by 35S radiosulafate incorporation and size analysis by SDS PAGE. Key findings: MTX had a concentration-dependent inhibitory effect on serum stimulated VSMC proliferation with a maximum and total inhibitory effect at 10 μM. Thrombin, platelet-derived growth factor and transforming growth factor beta stimulated proteoglycan synthesis and increased the size of the biglycan molecules but MTX (10 μM) had no effect on any of these responses. Conclusions: The outcome of a trial with MTX will reflect the potential of targeting inflammation for the prevention of atherosclerosis and it remains an interesting proposition to evaluate the effects of a “proteoglycan inhibitor” on atherosclerosis. OMICS International 2015-07 Article PeerReviewed application/pdf en http://irep.iium.edu.my/55384/1/9.%20Little%202015%20methotrexate-.pdf Little, Peter J. and Getachew, Robel and Kamato, Danielle and Rostam, Muhamad Ashraf and Cohen, Neale and Chan, Vincent and Osman, Narin (2015) Methotrexate inhibits proliferation but not proteoglycan synthesis or glycosaminoglycan hyperelongation in human vascular smooth muscle cells. Journal of Clinical & Experimental Pharmacology, 5 (4). pp. 1-6. ISSN 2161-1459 https://www.omicsonline.org/open-access/methotrexate-inhibits-proliferation-but-notproteoglycan-synthesis-or-glycosaminoglycan-hyperelongationin-human-vascular-smooth-muscle-cells-2161-1459-1000181.pdf 10.4172/2161-1459.1000181
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 Little, Peter J. Getachew, Robel Kamato, Danielle Rostam, Muhamad Ashraf Cohen, Neale Chan, Vincent Osman, Narin Methotrexate inhibits proliferation but not proteoglycan synthesis or glycosaminoglycan hyperelongation in human vascular smooth muscle cells
description	Objectives: Atherosclerosis is a disease process involving the early deposition of lipids in the vessel wall trapped by modified proteoglycans and subsequently a chronic inflammatory process leading to the clinical events. MTX has been chosen to study the potential efficacy of an anti inflammatory agent in preventing atherosclerosis and secondary cardiovascular disease in the cardiovascular inflammation reduction trial (CIRT). Methods: We have investigated cell proliferation and growth factor stimulated proteoglycan synthesis in vascular smooth muscle (VSMC) to assess some of the direct effects of MTX. Experiments were conducted in cultured human VSMC. Proliferation was assessed by the gold standard technique of cell counting and proteoglycan synthesis by 35S radiosulafate incorporation and size analysis by SDS PAGE. Key findings: MTX had a concentration-dependent inhibitory effect on serum stimulated VSMC proliferation with a maximum and total inhibitory effect at 10 μM. Thrombin, platelet-derived growth factor and transforming growth factor beta stimulated proteoglycan synthesis and increased the size of the biglycan molecules but MTX (10 μM) had no effect on any of these responses. Conclusions: The outcome of a trial with MTX will reflect the potential of targeting inflammation for the prevention of atherosclerosis and it remains an interesting proposition to evaluate the effects of a “proteoglycan inhibitor” on atherosclerosis.
format	Article
author	Little, Peter J. Getachew, Robel Kamato, Danielle Rostam, Muhamad Ashraf Cohen, Neale Chan, Vincent Osman, Narin
author_facet	Little, Peter J. Getachew, Robel Kamato, Danielle Rostam, Muhamad Ashraf Cohen, Neale Chan, Vincent Osman, Narin
author_sort	Little, Peter J.
title	Methotrexate inhibits proliferation but not proteoglycan synthesis or glycosaminoglycan hyperelongation in human vascular smooth muscle cells
title_short	Methotrexate inhibits proliferation but not proteoglycan synthesis or glycosaminoglycan hyperelongation in human vascular smooth muscle cells
title_full	Methotrexate inhibits proliferation but not proteoglycan synthesis or glycosaminoglycan hyperelongation in human vascular smooth muscle cells
title_fullStr	Methotrexate inhibits proliferation but not proteoglycan synthesis or glycosaminoglycan hyperelongation in human vascular smooth muscle cells
title_full_unstemmed	Methotrexate inhibits proliferation but not proteoglycan synthesis or glycosaminoglycan hyperelongation in human vascular smooth muscle cells
title_sort	methotrexate inhibits proliferation but not proteoglycan synthesis or glycosaminoglycan hyperelongation in human vascular smooth muscle cells
publisher	OMICS International
publishDate	2015
url	http://irep.iium.edu.my/55384/ http://irep.iium.edu.my/55384/ http://irep.iium.edu.my/55384/ http://irep.iium.edu.my/55384/1/9.%20Little%202015%20methotrexate-.pdf
first_indexed	2023-09-18T21:18:16Z
last_indexed	2023-09-18T21:18:16Z
_version_	1777411708895100928

Methotrexate inhibits proliferation but not proteoglycan synthesis or glycosaminoglycan hyperelongation in human vascular smooth muscle cells

Similar Items