title: Secreted Frizzled-related Protein 5 Diminishes Cardiac Inflammation and Protects the Heart from Ischemia/Reperfusion Injury.
abstract: Wnt signaling has diverse actions in cardiovascular development and disease processes. Secreted frizzled-related protein 5 (Sfrp5) has been shown to function as an extracellular inhibitor of non-canonical Wnt signaling that is expressed at relatively high levels in white adipose tissue. The aim of this study was to investigate the role of Sfrp5 in the heart under ischemic stress. Sfrp5 KO and WT mice were subjected to ischemia/reperfusion (I/R). Although Sfrp5-KO mice exhibited no detectable phenotype when compared with WT control at baseline, they displayed larger infarct sizes, enhanced cardiac myocyte apoptosis, and diminished cardiac function following I/R. The ischemic lesions of Sfrp5-KO mice had greater infiltration of Wnt5a-positive macrophages and greater inflammatory cytokine and chemokine gene expression when compared with WT mice. In bone marrow-derived macrophages, Wnt5a promoted JNK activation and increased inflammatory gene expression, whereas treatment with Sfrp5 blocked these effects. These results indicate that Sfrp5 functions to antagonize inflammatory responses after I/R in the heart, possibly through a mechanism involving non-canonical Wnt5a/JNK signaling.
authors.affiliation: From the Whitaker Cardiovascular Institute, Boston University Medical Campus, Boston, Massachusetts 02118 and.
authors.forename: Kazuto
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: From the Whitaker Cardiovascular Institute, Boston University Medical Campus, Boston, Massachusetts 02118 and.
authors.forename: Soichi
authors.initials: S
authors.lastname: Sano
authors.affiliation: From the Whitaker Cardiovascular Institute, Boston University Medical Campus, Boston, Massachusetts 02118 and.
authors.forename: José J
authors.initials: JJ
authors.lastname: Fuster
authors.affiliation: From the Whitaker Cardiovascular Institute, Boston University Medical Campus, Boston, Massachusetts 02118 and.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Kikuchi
authors.affiliation: From the Whitaker Cardiovascular Institute, Boston University Medical Campus, Boston, Massachusetts 02118 and.
authors.forename: Ippei
authors.initials: I
authors.lastname: Shimizu
authors.affiliation: From the Whitaker Cardiovascular Institute, Boston University Medical Campus, Boston, Massachusetts 02118 and.
authors.forename: Kousei
authors.initials: K
authors.lastname: Ohshima
authors.affiliation: From the Whitaker Cardiovascular Institute, Boston University Medical Campus, Boston, Massachusetts 02118 and.
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Katanasaka
authors.affiliation: From the Whitaker Cardiovascular Institute, Boston University Medical Campus, Boston, Massachusetts 02118 and the Department of Molecular Cardiovascular Medicine, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Ouchi
authors.affiliation: From the Whitaker Cardiovascular Institute, Boston University Medical Campus, Boston, Massachusetts 02118 and kxwalsh@bu.edu.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Walsh
mesh_terms: D000818:Animals; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D048670:MAP Kinase Kinase 4 / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D017202:Myocardial Ischemia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009205:Myocarditis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D000071818:Wnt-5a Protein
chemical_list: D008565:Membrane Proteins; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C438615:Wnt5a protein, mouse; D048670:MAP Kinase Kinase 4
keywords: Sfrp5; Wnt signaling; Wnt5a; c-Jun N-terminal kinase (JNK); macrophage; myocardial infarction; obesity