title: Wnt11 Gene Therapy with Adeno-associated Virus 9 Improves Recovery from Myocardial Infarction by Modulating the Inflammatory Response.
abstract: Acute myocardial infarction induces activation of the acute phase response and infiltration of leukocytes to the infarcted area. Moreover, myocardium that is remote from ischemic area also becomes inflamed. Inflammatory reaction clears dead cells and matrix debris, while prolongation or expansion of the inflammatory response results in dysfunction following myocardial infarction. Wnt glycolipoproteins are best characterized as regulators of embryonic development. Recently several reports suggest that they also contribute to the inflammatory response in adult animals. However, the effects of Wnt proteins on myocardial infarction have not been explored. Here we show that Wnt11 expression leads to significant improvements of survival and cardiac function by suppressing infiltration of multiple kinds of inflammatory cells in infarcted heart. Wnt11 protein suppresses gene expression of inflammatory cytokines through the modulation of NF-κB in vitro. These results reveal a novel function of Wnt11 in the regulation of inflammatory response and provide a rationale for the use of Wnt11 to manipulate human diseases that are mediated by inflammation.
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Morishita
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan.|Feinberg Cardiovascular Research Institute, Northwestern University School of Medicine, Chicago, IL 60611, USA.
authors.forename: Koichi
authors.initials: K
authors.lastname: Kobayashi
authors.affiliation: Feinberg Cardiovascular Research Institute, Northwestern University School of Medicine, Chicago, IL 60611, USA.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Klyachko
authors.affiliation: Feinberg Cardiovascular Research Institute, Northwestern University School of Medicine, Chicago, IL 60611, USA.|Tokyo Women's Medical University, Tokyo 162-0054, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Jujo
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan.
authors.forename: Kengo
authors.initials: K
authors.lastname: Maeda
authors.affiliation: Feinberg Cardiovascular Research Institute, Northwestern University School of Medicine, Chicago, IL 60611, USA.|Caladrius Biosciences, Inc. NJ 07920, USA.
authors.forename: Douglas W
authors.initials: DW
authors.lastname: Losordo
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan.
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Murohara
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D000229:Dependovirus / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage; D006801:Humans; D008297:Male; D051379:Mice; D009203:Myocardial Infarction / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D041681:NIH 3T3 Cells; D051153:Wnt Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: D016207:Cytokines; D051153:Wnt Proteins; C540523:Wnt11 protein, human