title: Elastin fragmentation and atherosclerosis progression: the elastokine concept.
abstract: Atherosclerosis is a progressive multifaceted inflammatory disease affecting large- and medium-sized arteries. Typical feature of this disease is the formation and build-up of atherosclerotic plaques characterized by vascular extracellular matrix degradation and remodeling. Many studies have documented degradation of native elastin, the main extracellular matrix protein responsible for resilience and elasticity of arteries, by local release of elastases, leading to the production of elastin-derived peptides (EDP). These peptides have been proposed to actively participate in the progression of the disease by accelerating different biological processes, such as LDL oxidation and calcification of the vascular wall. These pathophysiological effects are mediated by the binding of EDP on a peculiar heterotrimeric receptor named elastin receptor complex (ERC). In this article, we review the contribution of elastin in biological processes involved in atherosclerosis progression from its initial elastase-driven degradation to its ultimate cellular effects. Finally, we discuss the ERC and its derived signaling pathways as promising therapeutic targets.
authors.affiliation: Laboratoire Signalisation et Récepteurs Matriciels (SiRMa), FRE CNRS 3481 MEDyC, Université de Reims Champagne Ardenne, Faculté des Sciences Exactes et Naturelles, Reims, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Maurice
authors.forename: Sébastien
authors.initials: S
authors.lastname: Blaise
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Gayral
authors.forename: Laurent
authors.initials: L
authors.lastname: Debelle
authors.forename: Muriel
authors.initials: M
authors.lastname: Laffargue
authors.forename: William
authors.initials: W
authors.lastname: Hornebeck
authors.forename: Laurent
authors.initials: L
authors.lastname: Duca
mesh_terms: D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D050197:Atherosclerosis / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002317:Cardiovascular Agents / Q000627:therapeutic use; D018450:Disease Progression; D004549:Elastin / Q000378:metabolism*; D006801:Humans; D058990:Molecular Targeted Therapy; D010196:Pancreatic Elastase / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism*; D058226:Plaque, Atherosclerotic; D011956:Receptors, Cell Surface / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D002317:Cardiovascular Agents; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; C054901:elastin-binding proteins; D004549:Elastin; D010196:Pancreatic Elastase