title: Critical role of nucleotide-binding oligomerization domain-like receptor 3 in vascular repair.
abstract: Vascular remodeling characterized by hyperproliferative neointima formation is an unfavorable repair process that is triggered by vascular damage. This process is characterized by an increased local inflammatory and proliferative response that critically involves the pro-inflammatory cytokine interleukin-1β (IL-1β). IL-1β is expressed and cytosolically retained as a procytokine that requires additional processing prior to exerting its pro-inflammatory function. Maturation and release of pro IL-1β is governed by a cytosolic protein scaffold that is known as the inflammasome. Here we show that NLRP3 (NOD-like receptor family, pryin domain containing 3), an important activating component of the inflammasome, is involved in neointima formation after vascular injury. NLRP3 deficiency itself does not affect the functional cardiovascular phenotype and does not alter peripheral differential blood counts. However, neointima development following wire injury of the carotid artery was significantly decreased in NLRP3-deficient mice as compared to wild-type controls. In all, NLRP3 plays a non-redundant role in vascular damage mediated neointima formation. Our data establish NLRP3 as a key player in the response to vascular damage, which could open new avenues to therapeutic intervention.
authors.affiliation: Department of Medicine/Cardiology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Schlaweck
authors.forename: Sebastian
authors.initials: S
authors.lastname: Zimmer
authors.forename: Rafael
authors.initials: R
authors.lastname: Struck
authors.forename: Eva
authors.initials: E
authors.lastname: Bartok
authors.forename: Nikos
authors.initials: N
authors.lastname: Werner
authors.forename: Franz
authors.initials: F
authors.lastname: Bauernfeind
authors.forename: Eicke
authors.initials: E
authors.lastname: Latz
authors.forename: Georg
authors.initials: G
authors.lastname: Nickenig
authors.forename: Veit
authors.initials: V
authors.lastname: Hornung
authors.forename: Alexander
authors.initials: A
authors.lastname: Ghanem
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000293:injuries* / Q000378:metabolism / Q000473:pathology*; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D007249:Inflammation / Q000235:genetics / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D058426:Neointima / Q000235:genetics / Q000473:pathology*
chemical_list: D002352:Carrier Proteins; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse