title: Stretch of atrial myocytes stimulates recruitment of macrophages via ATP released through gap-junction channels.
abstract: Atrial inflammation is critical to atrial fibrillation initiation and progression. Although left atrial dilatation is a risk factor for atrial fibrillation, the mechanism linking atrial dilatation and inflammation is unclear. We evaluated the mechanisms underlying infiltration of macrophages induced by stretch of atrial myocytes. Murine macrophages were co-cultured with HL-1 murine atrial myocyte-derived cells. Mechanical stretch applied to atrial myocytes induced transwell macrophage migration. The gap junction-channel blocker carbenoxolone and the non-specific ATP-signaling modifiers apyrase and pyridoxal-phosphate-6-azophenyl-2',4'-disulfonate inhibited the enhanced migration. Mechanical stretch of atrial myocytes induced transient increase in extracellular ATP concentration, which was inhibited by carbenoxolone. siRNA knockdown of pannexin-2 inhibited ATP release and macrophage migration. Mice underwent transverse aortic constriction or sham procedure. Transverse aortic constriction procedure induced macrophage infiltration. Daily carbenoxolone administration significantly inhibited macrophage infiltration in the atrium. Thus, mechanical stretch of atrial myocytes induces macrophage migration by ATP released through gap-junction channels, at least in part, in vitro. Administering a gap junction family-channel blocker inhibited this inflammatory change in vivo.
authors.affiliation: Department of Bio-informational Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Sakiko
authors.initials: S
authors.lastname: Oishi
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Sasano
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Tateishi
authors.forename: Noriko
authors.initials: N
authors.lastname: Tamura
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Isobe
authors.forename: Tetsushi
authors.initials: T
authors.lastname: Furukawa
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001281:Atrial Fibrillation / Q000209:etiology / Q000473:pathology; D002229:Carbenoxolone / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D017630:Connexins / Q000037:antagonists & inhibitors / Q000502:physiology*; D017629:Gap Junctions / Q000378:metabolism*; D006325:Heart Atria / Q000166:cytology*; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D032383:Myocytes, Cardiac / Q000473:pathology*; D013314:Stress, Mechanical
chemical_list: D017630:Connexins; D000255:Adenosine Triphosphate; D002229:Carbenoxolone