{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T20:19:05Z","timestamp":1792527545207,"version":"4.5.0"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2010,3,19]]},"abstract":"<jats:p><jats:bold><jats:italic><jats:underline>Rationale:<\/jats:underline><\/jats:italic><\/jats:bold>The vasoactive peptide angiotensin II (Ang II) is a potent cardiotoxic hormone whose actions have been well studied, yet questions remain pertaining to the downstream factors that mediate its effects in cardiomyocytes.<\/jats:p><jats:p><jats:bold><jats:italic><jats:underline>Objective:<\/jats:underline><\/jats:italic><\/jats:bold>The in vivo role of the myocyte enhancer factor (MEF)2A target gene<jats:italic>Xirp2<\/jats:italic>in Ang II\u2013mediated cardiac remodeling was investigated.<\/jats:p><jats:p><jats:bold><jats:italic><jats:underline>Methods and Results:<\/jats:underline><\/jats:italic><\/jats:bold>Here we demonstrate that the MEF2A target gene<jats:italic>Xirp2<\/jats:italic>(also known as cardiomyopathy associated gene 3 [<jats:italic>CMYA3<\/jats:italic>]) is an important effector of the Ang II signaling pathway in the heart.<jats:italic>Xirp2<\/jats:italic>belongs to the evolutionarily conserved, muscle-specific, actin-binding<jats:italic>Xin<\/jats:italic>gene family and is significantly induced in the heart in response to systemic administration of Ang II. Initially, we characterized the<jats:italic>Xirp2<\/jats:italic>promoter and demonstrate that Ang II activates<jats:italic>Xirp2<\/jats:italic>expression by stimulating MEF2A transcriptional activity. To further characterize the role of Xirp2 downstream of Ang II signaling we generated mice harboring a hypomorphic allele of the<jats:italic>Xirp2<\/jats:italic>gene that resulted in a marked reduction in its expression in the heart. In the absence of Ang II, adult<jats:italic>Xirp2<\/jats:italic>hypomorphic mice displayed cardiac hypertrophy and increased \u03b2 myosin heavy chain expression. Strikingly,<jats:italic>Xirp2<\/jats:italic>hypomorphic mice chronically infused with Ang II exhibited altered pathological cardiac remodeling including an attenuated hypertrophic response, as well as diminished fibrosis and apoptosis.<\/jats:p><jats:p><jats:bold><jats:italic><jats:underline>Conclusions:<\/jats:underline><\/jats:italic><\/jats:bold>These findings reveal a novel MEF2A-Xirp2 pathway that functions downstream of Ang II signaling to modulate its pathological effects in the heart.<\/jats:p>","DOI":"10.1161\/circresaha.109.209007","type":"journal-article","created":{"date-parts":[[2010,1,22]],"date-time":"2010-01-22T03:07:41Z","timestamp":1264129661000},"page":"952-960","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":72,"title":["Modulation of Angiotensin II\u2013Mediated Cardiac Remodeling by the MEF2A Target Gene Xirp2"],"prefix":"10.1161","volume":"106","author":[{"given":"Sarah A.","family":"McCalmon","sequence":"first","affiliation":[{"name":"From the Department of Biology (S.A.M., D.M.D., K.S.D., C.M.S., O.M.K., M.M., E.P.E., F.J.N.), Program in Cell and Molecular Biology, Boston University; and Whitaker Cardiovascular Institute (S.A., K.S., K.O., K.W., H.G., F.J.N.) and Alapis Research Laboratories (H.G.), Boston University Medical School, Mass."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle M.","family":"Desjardins","sequence":"additional","affiliation":[{"name":"From the Department of Biology (S.A.M., D.M.D., K.S.D., C.M.S., O.M.K., M.M., E.P.E., F.J.N.), Program in Cell and Molecular Biology, Boston University; and Whitaker Cardiovascular Institute (S.A., K.S., K.O., K.W., H.G., F.J.N.) and Alapis Research Laboratories (H.G.), Boston University Medical School, Mass."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saad","family":"Ahmad","sequence":"additional","affiliation":[{"name":"From the Department of Biology (S.A.M., D.M.D., K.S.D., C.M.S., O.M.K., M.M., E.P.E., F.J.N.), Program in Cell and Molecular Biology, Boston University; and Whitaker Cardiovascular Institute (S.A., K.S., K.O., K.W., H.G., F.J.N.) and Alapis Research Laboratories (H.G.), Boston University Medical School, Mass."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharine S.","family":"Davidoff","sequence":"additional","affiliation":[{"name":"From the Department of Biology (S.A.M., D.M.D., K.S.D., C.M.S., O.M.K., M.M., E.P.E., F.J.N.), Program in Cell and Molecular Biology, Boston University; and Whitaker Cardiovascular Institute (S.A., K.S., K.O., K.W., H.G., F.J.N.) and Alapis Research Laboratories (H.G.), Boston University Medical School, Mass."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine M.","family":"Snyder","sequence":"additional","affiliation":[{"name":"From the Department of Biology (S.A.M., D.M.D., K.S.D., C.M.S., O.M.K., M.M., E.P.E., F.J.N.), Program in Cell and Molecular Biology, Boston University; and Whitaker Cardiovascular Institute (S.A., K.S., K.O., K.W., H.G., F.J.N.) and Alapis Research Laboratories (H.G.), Boston University Medical School, Mass."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaori","family":"Sato","sequence":"additional","affiliation":[{"name":"From the Department of Biology (S.A.M., D.M.D., K.S.D., C.M.S., O.M.K., M.M., E.P.E., F.J.N.), Program in Cell and Molecular Biology, Boston University; and Whitaker Cardiovascular Institute (S.A., K.S., K.O., K.W., H.G., F.J.N.) and Alapis Research Laboratories (H.G.), Boston University Medical School, Mass."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Ohashi","sequence":"additional","affiliation":[{"name":"From the Department of Biology (S.A.M., D.M.D., K.S.D., C.M.S., O.M.K., M.M., E.P.E., F.J.N.), Program in Cell and Molecular Biology, Boston University; and Whitaker Cardiovascular Institute (S.A., K.S., K.O., K.W., H.G., F.J.N.) and Alapis Research Laboratories (H.G.), Boston University Medical School, Mass."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ondra M.","family":"Kielbasa","sequence":"additional","affiliation":[{"name":"From the Department of Biology (S.A.M., D.M.D., K.S.D., C.M.S., O.M.K., M.M., E.P.E., F.J.N.), Program in Cell and Molecular Biology, Boston University; and Whitaker Cardiovascular Institute (S.A., K.S., K.O., K.W., H.G., F.J.N.) and Alapis Research Laboratories (H.G.), Boston University Medical School, Mass."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthen","family":"Mathew","sequence":"additional","affiliation":[{"name":"From the Department of Biology (S.A.M., D.M.D., K.S.D., C.M.S., O.M.K., M.M., E.P.E., F.J.N.), Program in Cell and Molecular Biology, Boston University; and Whitaker Cardiovascular Institute (S.A., K.S., K.O., K.W., H.G., F.J.N.) and Alapis Research Laboratories (H.G.), Boston University Medical School, Mass."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth P.","family":"Ewen","sequence":"additional","affiliation":[{"name":"From the Department of Biology (S.A.M., D.M.D., K.S.D., C.M.S., O.M.K., M.M., E.P.E., F.J.N.), Program in Cell and Molecular Biology, Boston University; and Whitaker Cardiovascular Institute (S.A., K.S., K.O., K.W., H.G., F.J.N.) and Alapis Research Laboratories (H.G.), Boston University Medical School, Mass."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Walsh","sequence":"additional","affiliation":[{"name":"From the Department of Biology (S.A.M., D.M.D., K.S.D., C.M.S., O.M.K., M.M., E.P.E., F.J.N.), Program in Cell and Molecular Biology, Boston University; and Whitaker Cardiovascular Institute (S.A., K.S., K.O., K.W., H.G., F.J.N.) and Alapis Research Laboratories (H.G.), Boston University Medical School, Mass."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haralambos","family":"Gavras","sequence":"additional","affiliation":[{"name":"From the Department of Biology (S.A.M., D.M.D., K.S.D., C.M.S., O.M.K., M.M., E.P.E., F.J.N.), Program in Cell and Molecular Biology, Boston University; and Whitaker Cardiovascular Institute (S.A., K.S., K.O., K.W., H.G., F.J.N.) and Alapis Research Laboratories (H.G.), Boston University Medical School, Mass."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco J.","family":"Naya","sequence":"additional","affiliation":[{"name":"From the Department of Biology (S.A.M., D.M.D., K.S.D., C.M.S., O.M.K., M.M., E.P.E., F.J.N.), Program in Cell and Molecular Biology, Boston University; and Whitaker Cardiovascular Institute (S.A., K.S., K.O., K.W., H.G., F.J.N.) and Alapis Research Laboratories (H.G.), Boston University Medical School, Mass."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(71)90008-0"},{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/S0031-6997(24)01434-0","volume":"52","year":"2000","unstructured":"Kim S, Iwao H. Molecular and cellular mechanisms of angiotensin II-mediated cardiovascular and renal diseases. Pharmacol Rev. 2000; 52: 11\u201334.","journal-title":"Pharmacol Rev"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00057.2004"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjhyper.2005.08.017"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M603244200"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm789"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0002857"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.01406"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.126.6.1281"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.10131"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00806.2007"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.18.012502.105840"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00749.2005"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R200021200"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M510499200"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.0000017629.70769.cc"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.0000134631.75684.4a"},{"key":"e_1_3_2_18_2","doi-asserted-by":"crossref","unstructured":"Bultman S Magnuson T. Classical genetics and gene targeting. In: Joyner AL ed. Gene Targeting: A Practical Approach. New York: Oxford University Press; 2000: 258\u2013260.","DOI":"10.1093\/oso\/9780199637928.003.0011"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1139\/o03-087"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1080\/152165401317190761"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3180001"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehp088"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1050-1738(02)00188-3"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.26.10.3875-3888.2006"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.0000018952.70505.f1"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0707659"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2004.07.121"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI12083"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10741-007-9034-1"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.231619298"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0808315106"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.02157-05"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2007.06.006"}],"container-title":["Circulation Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCRESAHA.109.209007","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,16]],"date-time":"2025-02-16T22:34:18Z","timestamp":1739745258000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCRESAHA.109.209007"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,3,19]]},"references-count":33,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2010,3,19]]}},"alternative-id":["10.1161\/CIRCRESAHA.109.209007"],"URL":"https:\/\/doi.org\/10.1161\/circresaha.109.209007","relation":{},"ISSN":["0009-7330","1524-4571"],"issn-type":[{"value":"0009-7330","type":"print"},{"value":"1524-4571","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,3,19]]},"assertion":[{"value":"2010-01-21","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}