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Molecular Mechanisms of Collagen Isotype-Specific Modulation of Smooth Muscle Cell Phenotype.

Orr, A Wayne; Lee, Monica Y; Lemmon, Julia A; Yurdagul, Arif; Gomez, Maria LU ; Schoppee Bortz, Pamela D and Wamhoff, Brian R (2009) In Arteriosclerosis, Thrombosis and Vascular Biology Nov 20. p.225-231
Abstract
OBJECTIVE: Smooth muscle cell (SMC) phenotypic modulation, an important component of atherosclerosis progression, is critically regulated by the matrix, with normal components of the healthy SMC matrix limiting modulation and atherosclerosis-associated transitional matrix proteins promoting phenotypic modulation. We sought to determine how collagen IV (which comprises the healthy artery wall) and monomeric collagen I (which comprises atherosclerotic lesions) differentially affect SMC phenotype. METHODS AND RESULTS: Plating SMCs on collagen IV resulted in elevated expression of SMC contractility proteins compared to collagen I. Concurrent with enhanced contractile gene expression, collagen IV stimulates binding of SRF to CArG boxes in the... (More)
OBJECTIVE: Smooth muscle cell (SMC) phenotypic modulation, an important component of atherosclerosis progression, is critically regulated by the matrix, with normal components of the healthy SMC matrix limiting modulation and atherosclerosis-associated transitional matrix proteins promoting phenotypic modulation. We sought to determine how collagen IV (which comprises the healthy artery wall) and monomeric collagen I (which comprises atherosclerotic lesions) differentially affect SMC phenotype. METHODS AND RESULTS: Plating SMCs on collagen IV resulted in elevated expression of SMC contractility proteins compared to collagen I. Concurrent with enhanced contractile gene expression, collagen IV stimulates binding of SRF to CArG boxes in the promoters of smooth muscle actin and smooth muscle myosin heavy chain. Coll IV also stimulated the expression of myocardin, a critical SRF coactivator required to drive expression of SMC specific genes. In contrast to collagen IV, collagen I stimulated enhanced expression of the inflammatory protein vascular cell adhesion molecule (VCAM)-1. NF-kappaB and NFAT-binding sites in the VCAM-1 promoter are critical for collagen I-mediated expression of VCAM-1 promoter activity. However, only inhibitors of NFAT, not NF-kappaB, were able to reduce collagen I-associated VCAM expression, and collagen I but not collagen IV stimulated NFAT transcriptional activity. CONCLUSIONS: These results show for the first time that collagen IV and collagen I differentially affect smooth muscle phenotypic modulation through multiple pathways. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Arteriosclerosis, Thrombosis and Vascular Biology
volume
Nov 20
pages
225 - 231
publisher
American Heart Association
external identifiers
  • wos:000262602200013
  • pmid:19023090
  • scopus:59449088249
ISSN
1524-4636
DOI
10.1161/ATVBAHA.108.178749
language
English
LU publication?
yes
id
867b1a0a-1534-4689-a1f9-f0efc9d680f9 (old id 1271251)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19023090?dopt=Abstract
date added to LUP
2008-12-04 16:16:33
date last changed
2017-09-03 04:50:37
@article{867b1a0a-1534-4689-a1f9-f0efc9d680f9,
  abstract     = {OBJECTIVE: Smooth muscle cell (SMC) phenotypic modulation, an important component of atherosclerosis progression, is critically regulated by the matrix, with normal components of the healthy SMC matrix limiting modulation and atherosclerosis-associated transitional matrix proteins promoting phenotypic modulation. We sought to determine how collagen IV (which comprises the healthy artery wall) and monomeric collagen I (which comprises atherosclerotic lesions) differentially affect SMC phenotype. METHODS AND RESULTS: Plating SMCs on collagen IV resulted in elevated expression of SMC contractility proteins compared to collagen I. Concurrent with enhanced contractile gene expression, collagen IV stimulates binding of SRF to CArG boxes in the promoters of smooth muscle actin and smooth muscle myosin heavy chain. Coll IV also stimulated the expression of myocardin, a critical SRF coactivator required to drive expression of SMC specific genes. In contrast to collagen IV, collagen I stimulated enhanced expression of the inflammatory protein vascular cell adhesion molecule (VCAM)-1. NF-kappaB and NFAT-binding sites in the VCAM-1 promoter are critical for collagen I-mediated expression of VCAM-1 promoter activity. However, only inhibitors of NFAT, not NF-kappaB, were able to reduce collagen I-associated VCAM expression, and collagen I but not collagen IV stimulated NFAT transcriptional activity. CONCLUSIONS: These results show for the first time that collagen IV and collagen I differentially affect smooth muscle phenotypic modulation through multiple pathways.},
  author       = {Orr, A Wayne and Lee, Monica Y and Lemmon, Julia A and Yurdagul, Arif and Gomez, Maria and Schoppee Bortz, Pamela D and Wamhoff, Brian R},
  issn         = {1524-4636},
  language     = {eng},
  pages        = {225--231},
  publisher    = {American Heart Association},
  series       = {Arteriosclerosis, Thrombosis and Vascular Biology},
  title        = {Molecular Mechanisms of Collagen Isotype-Specific Modulation of Smooth Muscle Cell Phenotype.},
  url          = {http://dx.doi.org/10.1161/ATVBAHA.108.178749},
  volume       = {Nov 20},
  year         = {2009},
}