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The small leucine-rich repeat proteoglycans in tissue repair and atherosclerosis.

Hultgårdh, Anna LU ; Borén, J and Chakravarti, S (2015) In Journal of Internal Medicine 278(5). p.447-461
Abstract
Proteoglycans consist of a protein core with one or more covalently attached glycosaminoglycan (GAG) side chains and have multiple roles in the initiation and progression of atherosclerosis. Here we discuss the potential and known functions of a group of small leucine-rich repeat proteoglycans (SLRPs) in atherosclerosis. We focus on five SLRPs, decorin, biglycan, lumican, fibromodulin and PRELP, because these have been detected in atherosclerotic plaques or demonstrated to have a role in animal models of atherosclerosis. Decorin and biglycan are modified post-translationally by substitution with chondroitin/dermatan sulphate GAGs, whereas lumican, fibromodulin and PRELP have keratan sulphate side chains, and the core proteins have... (More)
Proteoglycans consist of a protein core with one or more covalently attached glycosaminoglycan (GAG) side chains and have multiple roles in the initiation and progression of atherosclerosis. Here we discuss the potential and known functions of a group of small leucine-rich repeat proteoglycans (SLRPs) in atherosclerosis. We focus on five SLRPs, decorin, biglycan, lumican, fibromodulin and PRELP, because these have been detected in atherosclerotic plaques or demonstrated to have a role in animal models of atherosclerosis. Decorin and biglycan are modified post-translationally by substitution with chondroitin/dermatan sulphate GAGs, whereas lumican, fibromodulin and PRELP have keratan sulphate side chains, and the core proteins have leucine-rich repeat (LRR) motifs that are characteristic of the LRR superfamily. The chondroitin/dermatan sulphate GAG side chains have been implicated in lipid retention in atherosclerosis. The core proteins are discussed here in the context of (i) interactions with collagens and their implications in tissue integrity, fibrosis and wound repair and (ii) interactions with growth factors, cytokines, pathogen-associated molecular patterns and cell surface receptors that impact normal physiology and disease processes such as inflammation, innate immune responses and wound healing (i.e. processes that are all important in plaque development and progression). Thus, studies of these SLRPs in the context of wound healing are providing clues about their functions in early stages of atherosclerosis to plaque vulnerability and cardiovascular disease at later stages. Understanding of signal transduction pathways regulated by the core protein interactions is leading to novel roles and therapeutic potential for these proteins in wound repair and atherosclerosis. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Internal Medicine
volume
278
issue
5
pages
447 - 461
publisher
Wiley-Blackwell Publishing Ltd
external identifiers
  • pmid:26477596
  • wos:000363278500003
  • scopus:84944687983
ISSN
1365-2796
DOI
10.1111/joim.12400
language
English
LU publication?
yes
id
e30c5eb1-85d2-4d34-bead-e81f76e4619b (old id 8149061)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26477596?dopt=Abstract
date added to LUP
2015-11-03 16:09:37
date last changed
2017-09-17 03:04:48
@article{e30c5eb1-85d2-4d34-bead-e81f76e4619b,
  abstract     = {Proteoglycans consist of a protein core with one or more covalently attached glycosaminoglycan (GAG) side chains and have multiple roles in the initiation and progression of atherosclerosis. Here we discuss the potential and known functions of a group of small leucine-rich repeat proteoglycans (SLRPs) in atherosclerosis. We focus on five SLRPs, decorin, biglycan, lumican, fibromodulin and PRELP, because these have been detected in atherosclerotic plaques or demonstrated to have a role in animal models of atherosclerosis. Decorin and biglycan are modified post-translationally by substitution with chondroitin/dermatan sulphate GAGs, whereas lumican, fibromodulin and PRELP have keratan sulphate side chains, and the core proteins have leucine-rich repeat (LRR) motifs that are characteristic of the LRR superfamily. The chondroitin/dermatan sulphate GAG side chains have been implicated in lipid retention in atherosclerosis. The core proteins are discussed here in the context of (i) interactions with collagens and their implications in tissue integrity, fibrosis and wound repair and (ii) interactions with growth factors, cytokines, pathogen-associated molecular patterns and cell surface receptors that impact normal physiology and disease processes such as inflammation, innate immune responses and wound healing (i.e. processes that are all important in plaque development and progression). Thus, studies of these SLRPs in the context of wound healing are providing clues about their functions in early stages of atherosclerosis to plaque vulnerability and cardiovascular disease at later stages. Understanding of signal transduction pathways regulated by the core protein interactions is leading to novel roles and therapeutic potential for these proteins in wound repair and atherosclerosis.},
  author       = {Hultgårdh, Anna and Borén, J and Chakravarti, S},
  issn         = {1365-2796},
  language     = {eng},
  number       = {5},
  pages        = {447--461},
  publisher    = {Wiley-Blackwell Publishing Ltd},
  series       = {Journal of Internal Medicine},
  title        = {The small leucine-rich repeat proteoglycans in tissue repair and atherosclerosis.},
  url          = {http://dx.doi.org/10.1111/joim.12400},
  volume       = {278},
  year         = {2015},
}