@article{b03999c1f83a45beab7fc044035de9ba,
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-K B 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.",
author = "Yoshihiro Morishita and Koichi Kobayashi and Ekaterina Klyachko and Kentaro Jujo and Kengo Maeda and Losordo, {Douglas W.} and Toyoaki Murohara",
note = "Funding Information: We thank Sol Misener, Aiko Ito, Trevor Clarke, Meredith Millay, Christine Kamide, Andrew Scarpelli, and Yoko Inoue for their excellent technical assistance, Masaaki Ii for scientific advice, Ashley Peterson for administrative assistance, W. Kevin Meisner, PhD, ELS, for editorial support, Hiroyuki Nakai (Department of Microbiology and Molecular Genetics, University of Pittsburg School of Medicine, Pittsburgh, USA) for scientific advice to produce the adeno-associated virus 9, and the University of Pennsylvania Vector Core for providing us with AAV2/9 capsid plasmid. We would like to acknowledge the Gene Therapy Resource Program (GTRP) of the National Heart, Lung and Blood Institute, National Institutes of Health for providing the gene vectors used in this study. NIH grants HL-53354, HL-77428, HL-63414, HL-80137, HL-95874, HLPO1-66957, and HL-57516. Grants (No. 23390208, and 20249045 to Toyoaki Murohara) from the Ministry of Education, Culture, Sports, Science and Technology of Japan. Grant-in-Aid for Young Scientists B and grant from Suzuken Memorial Foundation, Japan (to Koichi Kobayashi). There are no relationships with industry in the experiment.",
year = "2016",
month = feb,
day = "17",
doi = "10.1038/srep21705",
language = "English (US)",
volume = "6",
journal = "Scientific reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
}
