{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T14:47:35Z","timestamp":1771512455713,"version":"3.50.1"},"reference-count":38,"publisher":"Elsevier BV","issue":"9","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2016,10,7]],"date-time":"2016-10-07T00:00:00Z","timestamp":1475798400000},"content-version":"vor","delay-in-days":402,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Therapy"],"published-print":{"date-parts":[[2015,9]]},"DOI":"10.1038\/mt.2015.92","type":"journal-article","created":{"date-parts":[[2015,5,22]],"date-time":"2015-05-22T07:22:30Z","timestamp":1432279350000},"page":"1434-1443","source":"Crossref","is-referenced-by-count":64,"title":["ACE2 Therapy Using Adeno-associated Viral Vector Inhibits Liver Fibrosis in Mice"],"prefix":"10.1016","volume":"23","author":[{"given":"Kai Y","family":"Mak","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruth","family":"Chin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharon C","family":"Cunningham","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miriam R","family":"Habib","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph","family":"Torresi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandra F","family":"Sharland","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ian E","family":"Alexander","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter W","family":"Angus","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chandana B","family":"Herath","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1038\/mt.2015.92_bib1","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1016\/j.jhep.2007.01.025","article-title":"Worldwide mortality from cirrhosis: an update to 2002","volume":"46","author":"Bosetti","year":"2007","journal-title":"J Hepatol"},{"key":"10.1038\/mt.2015.92_bib2","doi-asserted-by":"crossref","first-page":"1887","DOI":"10.1172\/JCI66028","article-title":"Evolving therapies for liver fibrosis","volume":"123","author":"Schuppan","year":"2013","journal-title":"J Clin Invest"},{"key":"10.1038\/mt.2015.92_bib3","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1002\/hep.20665","article-title":"Systemic infusion of angiotensin II exacerbates liver fibrosis in bile duct-ligated rats","volume":"41","author":"Bataller","year":"2005","journal-title":"Hepatology"},{"key":"10.1038\/mt.2015.92_bib4","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1016\/S0016-5085(00)70368-4","article-title":"Angiotensin II induces contraction and proliferation of human hepatic stellate cells","volume":"118","author":"Bataller","year":"2000","journal-title":"Gastroenterology"},{"key":"10.1038\/mt.2015.92_bib5","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1172\/JCI18212","article-title":"NADPH oxidase signal transduces angiotensin II in hepatic stellate cells and is critical in hepatic fibrosis","volume":"112","author":"Bataller","year":"2003","journal-title":"J Clin Invest"},{"key":"10.1038\/mt.2015.92_bib6","doi-asserted-by":"crossref","first-page":"G726","DOI":"10.1152\/ajpgi.00162.2009","article-title":"Effects of losartan on hepatic expression of nonphagocytic NADPH oxidase and fibrogenic genes in patients with chronic hepatitis C","volume":"297","author":"Colmenero","year":"2009","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"10.1038\/mt.2015.92_bib7","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1053\/jhep.2002.32679","article-title":"Effect of angiotensin receptor antagonist on liver fibrosis in early stages of chronic hepatitis C","volume":"36","author":"Terui","year":"2002","journal-title":"Hepatology"},{"key":"10.1038\/mt.2015.92_bib8","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1097\/MNH.0b013e328031f362","article-title":"Angiotensin-(1-7) and the renin-angiotensin system","volume":"16","author":"Santos","year":"2007","journal-title":"Curr Opin Nephrol Hypertens"},{"key":"10.1038\/mt.2015.92_bib9","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1042\/CS20080647","article-title":"Angiotensin-(1-7), an alternative metabolite of the renin-angiotensin system, is up-regulated in human liver disease and has antifibrotic activity in the bile-duct-ligated rat","volume":"117","author":"Lubel","year":"2009","journal-title":"Clin Sci (Lond)"},{"key":"10.1038\/mt.2015.92_bib10","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1002\/hep.23104","article-title":"Angiotensin-converting-enzyme 2 inhibits liver fibrosis in mice","volume":"50","author":"Osterreicher","year":"2009","journal-title":"Hepatology"},{"key":"10.1038\/mt.2015.92_bib11","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1053\/j.gastro.2013.06.036","article-title":"Activation of the MAS receptor by angiotensin-(1-7) in the renin-angiotensin system mediates mesenteric vasodilatation in cirrhosis","volume":"145","author":"Grace","year":"2013","journal-title":"Gastroenterology"},{"key":"10.1038\/mt.2015.92_bib12","doi-asserted-by":"crossref","first-page":"G98","DOI":"10.1152\/ajpgi.00045.2009","article-title":"Portal pressure responses and angiotensin peptide production in rat liver are determined by relative activity of ACE and ACE2","volume":"297","author":"Herath","year":"2009","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"10.1038\/mt.2015.92_bib13","doi-asserted-by":"crossref","first-page":"G99","DOI":"10.1152\/ajpgi.00163.2012","article-title":"Angiotensin-(1-7) reduces the perfusion pressure response to angiotensin II and methoxamine via an endothelial nitric oxide-mediated pathway in cirrhotic rat liver","volume":"304","author":"Herath","year":"2013","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"10.1038\/mt.2015.92_bib14","doi-asserted-by":"crossref","first-page":"S98","DOI":"10.1111\/j.1440-1746.2007.05277.x","article-title":"Oxidative stress in alcoholic liver disease: role of NADPH oxidase complex","volume":"23 Suppl 1","author":"De Minicis","year":"2008","journal-title":"J Gastroenterol Hepatol"},{"key":"10.1038\/mt.2015.92_bib15","doi-asserted-by":"crossref","first-page":"1730","DOI":"10.1002\/hep.24281","article-title":"The nicotinamide adenine dinucleotide phosphate oxidase (NOX) homologues NOX1 and NOX2\/gp91(phox) mediate hepatic fibrosis in mice","volume":"53","author":"Paik","year":"2011","journal-title":"Hepatology"},{"key":"10.1038\/mt.2015.92_bib16","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.cardiores.2004.08.007","article-title":"Vascular NADPH oxidases: molecular mechanisms of activation","volume":"65","author":"Brandes","year":"2005","journal-title":"Cardiovasc Res"},{"key":"10.1038\/mt.2015.92_bib17","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1113\/expphysiol.2012.067165","article-title":"Angiotensin-converting enzyme 2 antagonizes angiotensin II-induced pressor response and NADPH oxidase activation in Wistar-Kyoto rats and spontaneously hypertensive rats","volume":"98","author":"Lo","year":"2013","journal-title":"Exp Physiol"},{"key":"10.1038\/mt.2015.92_bib18","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.mam.2007.09.016","article-title":"4-Hydroxynonenal-protein adducts: A reliable biomarker of lipid oxidation in liver diseases","volume":"29","author":"Poli","year":"2008","journal-title":"Mol Aspects Med"},{"key":"10.1038\/mt.2015.92_bib19","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1002\/bies.950180708","article-title":"Protein kinase cascades activated by stress and inflammatory cytokines","volume":"18","author":"Kyriakis","year":"1996","journal-title":"Bioessays"},{"key":"10.1038\/mt.2015.92_bib20","doi-asserted-by":"crossref","first-page":"1743","DOI":"10.1038\/sj.bjp.0704630","article-title":"Angiotensin-(1-7) is involved in the endothelium-dependent modulation of phenylephrine-induced contraction in the aorta of mRen-2 transgenic rats","volume":"135","author":"Lemos","year":"2002","journal-title":"Br J Pharmacol"},{"key":"10.1038\/mt.2015.92_bib21","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.1053\/gast.2002.36561","article-title":"Up-regulation of components of the renin-angiotensin system in the bile duct-ligated rat liver","volume":"123","author":"Paizis","year":"2002","journal-title":"Gastroenterology"},{"key":"10.1038\/mt.2015.92_bib22","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.jhep.2007.03.008","article-title":"Upregulation of hepatic angiotensin-converting enzyme 2 (ACE2) and angiotensin-(1-7) levels in experimental biliary fibrosis","volume":"47","author":"Herath","year":"2007","journal-title":"J Hepatol"},{"key":"10.1038\/mt.2015.92_bib23","doi-asserted-by":"crossref","first-page":"H736","DOI":"10.1152\/ajpheart.00937.2006","article-title":"Prevention of angiotensin II-induced cardiac remodeling by angiotensin-(1-7)","volume":"292","author":"Grobe","year":"2007","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"10.1038\/mt.2015.92_bib24","doi-asserted-by":"crossref","first-page":"H801","DOI":"10.1152\/ajpheart.00908.2011","article-title":"Angiotensin-(1-7) attenuates angiotensin II-induced cardiac remodeling associated with upregulation of dual-specificity phosphatase 1","volume":"302","author":"McCollum","year":"2012","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"10.1038\/mt.2015.92_bib25","doi-asserted-by":"crossref","first-page":"e00264","DOI":"10.1002\/phy2.264","article-title":"ACE2 deficiency increases NADPH-mediated oxidative stress in the kidney","volume":"2","author":"Wysocki","year":"2014","journal-title":"Physiol Rep"},{"key":"10.1038\/mt.2015.92_bib26","doi-asserted-by":"crossref","first-page":"F812","DOI":"10.1152\/ajprenal.00655.2013","article-title":"Angiotensin 1-7 mediates renoprotection against diabetic nephropathy by reducing oxidative stress, inflammation, and lipotoxicity","volume":"306","author":"Mori","year":"2014","journal-title":"Am J Physiol Renal Physiol"},{"key":"10.1038\/mt.2015.92_bib27","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.peptides.2013.05.010","article-title":"Oral Angiotensin-(1-7) prevented obesity and hepatic inflammation by inhibition of resistin\/TLR4\/MAPK\/NF-\u03baB in rats fed with high-fat diet","volume":"46","author":"Santos","year":"2013","journal-title":"Peptides"},{"key":"10.1038\/mt.2015.92_bib28","doi-asserted-by":"crossref","first-page":"2212","DOI":"10.1038\/sj.ki.5001509","article-title":"Angiotensin-(1-7) inhibits angiotensin II-stimulated phosphorylation of MAP kinases in proximal tubular cells","volume":"69","author":"Su","year":"2006","journal-title":"Kidney Int"},{"key":"10.1038\/mt.2015.92_bib29","doi-asserted-by":"crossref","first-page":"C1169","DOI":"10.1152\/ajpcell.00145.2008","article-title":"MAP kinase\/phosphatase pathway mediates the regulation of ACE2 by angiotensin peptides","volume":"295","author":"Gallagher","year":"2008","journal-title":"Am J Physiol Cell Physiol"},{"key":"10.1038\/mt.2015.92_bib30","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1016\/0016-5085(94)90233-X","article-title":"Vascular hyporesponsiveness to endothelin 1 in rats with cirrhosis","volume":"107","author":"Hartleb","year":"1994","journal-title":"Gastroenterology"},{"key":"10.1038\/mt.2015.92_bib31","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/S0016-5085(99)70136-8","article-title":"Altered adrenergic responsiveness of endothelium-denuded hepatic arteries and portal veins in patients with cirrhosis","volume":"116","author":"Heller","year":"1999","journal-title":"Gastroenterology"},{"key":"10.1038\/mt.2015.92_bib32","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1053\/j.gastro.2005.11.029","article-title":"Defective RhoA\/Rho-kinase signaling contributes to vascular hypocontractility and vasodilation in cirrhotic rats","volume":"130","author":"Hennenberg","year":"2006","journal-title":"Gastroenterology"},{"key":"10.1038\/mt.2015.92_bib33","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1111\/j.1365-2362.2009.02181.x","article-title":"Vascular hyporesponsiveness to angiotensin II in rats with CCl(4)-induced liver cirrhosis","volume":"39","author":"Hennenberg","year":"2009","journal-title":"Eur J Clin Invest"},{"key":"10.1038\/mt.2015.92_bib34","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1038\/mt.2008.72","article-title":"Gene delivery to the juvenile mouse liver using AAV2\/8 vectors","volume":"16","author":"Cunningham","year":"2008","journal-title":"Mol Ther"},{"key":"10.1038\/mt.2015.92_bib35","doi-asserted-by":"crossref","first-page":"17158","DOI":"10.1073\/pnas.0909520106","article-title":"Distinct immune responses to transgene products from rAAV1 and rAAV8 vectors","volume":"106","author":"Lu","year":"2009","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1038\/mt.2015.92_bib36","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1038\/gt.2012.67","article-title":"Comparison of gene transfer to the murine liver following intraperitoneal and intraportal delivery of hepatotropic AAV pseudo-serotypes","volume":"20","author":"Dane","year":"2013","journal-title":"Gene Ther"},{"key":"10.1038\/mt.2015.92_bib37","doi-asserted-by":"crossref","first-page":"2357","DOI":"10.1056\/NEJMoa1108046","article-title":"Adenovirus-associated virus vector-mediated gene transfer in hemophilia B","volume":"365","author":"Nathwani","year":"2011","journal-title":"N Engl J Med"},{"key":"10.1038\/mt.2015.92_bib38","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1111\/jgh.12042","article-title":"Advanced glycation end products augment experimental hepatic fibrosis","volume":"28","author":"Goodwin","year":"2013","journal-title":"J Gastroenterol Hepatol"}],"container-title":["Molecular Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1525001616302714?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1525001616302714?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2018,9,22]],"date-time":"2018-09-22T07:55:33Z","timestamp":1537602933000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1525001616302714"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,9]]},"references-count":38,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2015,9]]}},"alternative-id":["S1525001616302714"],"URL":"https:\/\/doi.org\/10.1038\/mt.2015.92","relation":{},"ISSN":["1525-0016"],"issn-type":[{"value":"1525-0016","type":"print"}],"subject":[],"published":{"date-parts":[[2015,9]]}}}