{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T21:10:14Z","timestamp":1791407414642,"version":"4.3.3"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2012,12,23]],"date-time":"2012-12-23T00:00:00Z","timestamp":1356220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nat Med"],"published-print":{"date-parts":[[2013,1]]},"DOI":"10.1038\/nm.3040","type":"journal-article","created":{"date-parts":[[2012,12,23]],"date-time":"2012-12-23T19:49:48Z","timestamp":1356292188000},"page":"74-82","source":"Crossref","is-referenced-by-count":322,"title":["An endothelial apelin-FGF link mediated by miR-424 and miR-503 is disrupted in pulmonary arterial hypertension"],"prefix":"10.1038","volume":"19","author":[{"given":"Jongmin","family":"Kim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujung","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoko","family":"Kojima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet K","family":"Lighthouse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyue","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micheala A","family":"Aldred","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle L","family":"McLean","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyekyung","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzy A","family":"Comhair","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel M","family":"Greif","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serpil C","family":"Erzurum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyung J","family":"Chun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2012,12,23]]},"reference":[{"key":"BFnm3040_CR1","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.ccm.2006.11.010","volume":"28","author":"RM Tuder","year":"2007","unstructured":"Tuder, R.M., Marecki, J.C., Richter, A., Fijalkowska, I. & Flores, S. Pathology of pulmonary hypertension. Clin. Chest Med. 28, 23\u201342, vii (2007).","journal-title":"Clin. Chest Med."},{"key":"BFnm3040_CR2","doi-asserted-by":"publisher","first-page":"13S","DOI":"10.1016\/j.jacc.2004.02.029","volume":"43","author":"M Humbert","year":"2004","unstructured":"Humbert, M. et al. Cellular and molecular pathobiology of pulmonary arterial hypertension. J. Am. Coll. Cardiol. 43, 13S\u201324S (2004).","journal-title":"J. Am. Coll. Cardiol."},{"key":"BFnm3040_CR3","doi-asserted-by":"publisher","first-page":"S10","DOI":"10.1016\/j.jacc.2009.04.006","volume":"54","author":"PM Hassoun","year":"2009","unstructured":"Hassoun, P.M. et al. Inflammation, growth factors, and pulmonary vascular remodeling. J. Am. Coll. Cardiol. 54, S10\u2013S19 (2009).","journal-title":"J. Am. Coll. Cardiol."},{"key":"BFnm3040_CR4","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1038\/nrcardio.2011.87","volume":"8","author":"RT Schermuly","year":"2011","unstructured":"Schermuly, R.T., Ghofrani, H.A., Wilkins, M.R. & Grimminger, F. Mechanisms of disease: pulmonary arterial hypertension. Nat. Rev. Cardiol. 8, 443\u2013455 (2011).","journal-title":"Nat. Rev. Cardiol."},{"key":"BFnm3040_CR5","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1172\/JCI35070","volume":"119","author":"M Izikki","year":"2009","unstructured":"Izikki, M. et al. Endothelial-derived FGF2 contributes to the progression of pulmonary hypertension in humans and rodents. J. Clin. Invest. 119, 512\u2013523 (2009).","journal-title":"J. Clin. Invest."},{"key":"BFnm3040_CR6","doi-asserted-by":"publisher","first-page":"1857","DOI":"10.1161\/CIRCULATIONAHA.105.591321","volume":"113","author":"S Eddahibi","year":"2006","unstructured":"Eddahibi, S. et al. Cross talk between endothelial and smooth muscle cells in pulmonary hypertension: critical role for serotonin-induced smooth muscle hyperplasia. Circulation 113, 1857\u20131864 (2006).","journal-title":"Circulation"},{"key":"BFnm3040_CR7","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1164\/rccm.200602-304OC","volume":"174","author":"L Dewachter","year":"2006","unstructured":"Dewachter, L. et al. Angiopoietin\/Tie2 pathway influences smooth muscle hyperplasia in idiopathic pulmonary hypertension. Am. J. Respir. Crit. Care Med. 174, 1025\u20131033 (2006).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"BFnm3040_CR8","doi-asserted-by":"publisher","first-page":"814","DOI":"10.1161\/ATVBAHA.110.219980","volume":"31","author":"SM Chandra","year":"2011","unstructured":"Chandra, S.M. et al. Disruption of the apelin-APJ system worsens hypoxia-induced pulmonary hypertension. Arterioscler. Thromb. Vasc. Biol. 31, 814\u2013820 (2011).","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"BFnm3040_CR9","doi-asserted-by":"publisher","first-page":"3735","DOI":"10.1172\/JCI43382","volume":"121","author":"TP Alastalo","year":"2011","unstructured":"Alastalo, T.P. et al. Disruption of PPAR\u03b3\/\u03b2-catenin-mediated regulation of apelin impairs BMP-induced mouse and human pulmonary arterial EC survival. J. Clin. Invest. 121, 3735\u20133746 (2011).","journal-title":"J. Clin. Invest."},{"key":"BFnm3040_CR10","doi-asserted-by":"publisher","first-page":"H88","DOI":"10.1152\/ajpheart.00935.2007","volume":"294","author":"AY Sheikh","year":"2008","unstructured":"Sheikh, A.Y. et al. In vivo genetic profiling and cellular localization of apelin reveals a hypoxia-sensitive, endothelial-centered pathway activated in ischemic heart failure. Am. J. Physiol. Heart Circ. Physiol. 294, H88\u2013H98 (2008).","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"BFnm3040_CR11","doi-asserted-by":"publisher","first-page":"21061","DOI":"10.1074\/jbc.M908417199","volume":"275","author":"M Hosoya","year":"2000","unstructured":"Hosoya, M. et al. Molecular and functional characteristics of APJ. Tissue distribution of mRNA and interaction with the endogenous ligand apelin. J. Biol. Chem. 275, 21061\u201321067 (2000).","journal-title":"J. Biol. Chem."},{"key":"BFnm3040_CR12","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1016\/j.cell.2008.08.040","volume":"135","author":"JB Regard","year":"2008","unstructured":"Regard, J.B., Sato, I.T. & Coughlin, S.R. Anatomical profiling of G protein\u2013coupled receptor expression. Cell 135, 561\u2013571 (2008).","journal-title":"Cell"},{"key":"BFnm3040_CR13","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1016\/j.regpep.2005.09.032","volume":"133","author":"JP Goetze","year":"2006","unstructured":"Goetze, J.P. et al. Apelin: a new plasma marker of cardiopulmonary disease. Regul. Pept. 133, 134\u2013138 (2006).","journal-title":"Regul. Pept."},{"key":"BFnm3040_CR14","first-page":"275","volume":"144","author":"RM Tuder","year":"1994","unstructured":"Tuder, R.M., Groves, B., Badesch, D.B. & Voelkel, N.F. Exuberant endothelial cell growth and elements of inflammation are present in plexiform lesions of pulmonary hypertension. Am. J. Pathol. 144, 275\u2013285 (1994).","journal-title":"Am. J. Pathol."},{"key":"BFnm3040_CR15","doi-asserted-by":"publisher","first-page":"L548","DOI":"10.1152\/ajplung.00428.2006","volume":"293","author":"FA Masri","year":"2007","unstructured":"Masri, F.A. et al. Hyperproliferative apoptosis-resistant endothelial cells in idiopathic pulmonary arterial hypertension. Am. J. Physiol. Lung Cell. Mol. Physiol. 293, L548\u2013L554 (2007).","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"BFnm3040_CR16","doi-asserted-by":"publisher","first-page":"1255","DOI":"10.1378\/chest.126.4.1255","volume":"126","author":"JI Benisty","year":"2004","unstructured":"Benisty, J.I. et al. Elevated basic fibroblast growth factor levels in patients with pulmonary arterial hypertension. Chest 126, 1255\u20131261 (2004).","journal-title":"Chest"},{"key":"BFnm3040_CR17","doi-asserted-by":"publisher","first-page":"H2007","DOI":"10.1152\/ajpheart.00089.2009","volume":"296","author":"I Falc\u00e3o-Pires","year":"2009","unstructured":"Falc\u00e3o-Pires, I. et al. Apelin decreases myocardial injury and improves right ventricular function in monocrotaline-induced pulmonary hypertension. Am. J. Physiol. Heart Circ. Physiol. 296, H2007\u2013H2014 (2009).","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"BFnm3040_CR18","doi-asserted-by":"publisher","first-page":"H1904","DOI":"10.1152\/ajpheart.00686.2009","volume":"297","author":"DN Charo","year":"2009","unstructured":"Charo, D.N. et al. Endogenous regulation of cardiovascular function by apelin-APJ. Am. J. Physiol. Heart Circ. Physiol. 297, H1904\u2013H1913 (2009).","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"BFnm3040_CR19","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/S0167-4889(99)00114-7","volume":"1452","author":"Y Habata","year":"1999","unstructured":"Habata, Y. et al. Apelin, the natural ligand of the orphan receptor APJ, is abundantly secreted in the colostrum. Biochim. Biophys. Acta 1452, 25\u201335 (1999).","journal-title":"Biochim. Biophys. Acta"},{"key":"BFnm3040_CR20","doi-asserted-by":"publisher","first-page":"2595","DOI":"10.1161\/ATVBAHA.111.236521","volume":"31","author":"A Chamorro-Jorganes","year":"2011","unstructured":"Chamorro-Jorganes, A. et al. MicroRNA-16 and microRNA-424 regulate cell-autonomous angiogenic functions in endothelial cells via targeting vascular endothelial growth factor receptor-2 and fibroblast growth factor receptor-1. Arterioscler. Thromb. Vasc. Biol. 31, 2595\u20132606 (2011).","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"BFnm3040_CR21","doi-asserted-by":"publisher","first-page":"3355","DOI":"10.1172\/JCI35298","volume":"118","author":"M Murakami","year":"2008","unstructured":"Murakami, M. et al. The FGF system has a key role in regulating vascular integrity. J. Clin. Invest. 118, 3355\u20133366 (2008).","journal-title":"J. Clin. Invest."},{"key":"BFnm3040_CR22","doi-asserted-by":"publisher","first-page":"L1013","DOI":"10.1152\/ajplung.00217.2009","volume":"297","author":"KR Stenmark","year":"2009","unstructured":"Stenmark, K.R., Meyrick, B., Galie, N., Mooi, W.J. & McMurtry, I.F. Animal models of pulmonary arterial hypertension: the hope for etiological discovery and pharmacological cure. Am. J. Physiol. Lung Cell. Mol. Physiol. 297, L1013\u2013L1032 (2009).","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"BFnm3040_CR23","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1096\/fj.00-0343com","volume":"15","author":"L Taraseviciene-Stewart","year":"2001","unstructured":"Taraseviciene-Stewart, L. et al. Inhibition of the VEGF receptor 2 combined with chronic hypoxia causes cell death\u2013dependent pulmonary endothelial cell proliferation and severe pulmonary hypertension. FASEB J. 15, 427\u2013438 (2001).","journal-title":"FASEB J."},{"key":"BFnm3040_CR24","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1165\/rcmb.2010-0317OC","volume":"45","author":"L Tu","year":"2011","unstructured":"Tu, L. et al. Autocrine fibroblast growth factor-2 signaling contributes to altered endothelial phenotype in pulmonary hypertension. Am. J. Respir. Cell Mol. Biol. 45, 311\u2013322 (2011).","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"BFnm3040_CR25","doi-asserted-by":"publisher","first-page":"1909","DOI":"10.1096\/fj.04-1930fje","volume":"18","author":"B Masri","year":"2004","unstructured":"Masri, B., Morin, N., Cornu, M., Knibiehler, B. & Audigier, Y. Apelin (65\u201377) activates p70 S6 kinase and is mitogenic for umbilical endothelial cells. FASEB J. 18, 1909\u20131911 (2004).","journal-title":"FASEB J."},{"key":"BFnm3040_CR26","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1161\/CIRCRESAHA.108.179333","volume":"103","author":"M Eyries","year":"2008","unstructured":"Eyries, M. et al. Hypoxia-induced apelin expression regulates endothelial cell proliferation and regenerative angiogenesis. Circ. Res. 103, 432\u2013440 (2008).","journal-title":"Circ. Res."},{"key":"BFnm3040_CR27","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1016\/j.ydbio.2007.03.004","volume":"305","author":"RE K\u00e4lin","year":"2007","unstructured":"K\u00e4lin, R.E. et al. Paracrine and autocrine mechanisms of apelin signaling govern embryonic and tumor angiogenesis. Dev. Biol. 305, 599\u2013614 (2007).","journal-title":"Dev. Biol."},{"key":"BFnm3040_CR28","doi-asserted-by":"publisher","first-page":"4025","DOI":"10.1182\/blood-2010-02-270819","volume":"116","author":"R del Toro","year":"2010","unstructured":"del Toro, R. et al. Identification and functional analysis of endothelial tip cell-enriched genes. Blood 116, 4025\u20134033 (2010).","journal-title":"Blood"},{"key":"BFnm3040_CR29","doi-asserted-by":"publisher","first-page":"2182","DOI":"10.1161\/ATVBAHA.110.209775","volume":"30","author":"A Kasai","year":"2010","unstructured":"Kasai, A. et al. Apelin is a crucial factor for hypoxia-induced retinal angiogenesis. Arterioscler. Thromb. Vasc. Biol. 30, 2182\u20132187 (2010).","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"BFnm3040_CR30","doi-asserted-by":"publisher","first-page":"1717","DOI":"10.1161\/ATVBAHA.108.163402","volume":"28","author":"A Kasai","year":"2008","unstructured":"Kasai, A. et al. Retardation of retinal vascular development in apelin-deficient mice. Arterioscler. Thromb. Vasc. Biol. 28, 1717\u20131722 (2008).","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"BFnm3040_CR31","doi-asserted-by":"publisher","first-page":"3166","DOI":"10.1182\/blood-2009-07-232306","volume":"115","author":"H Kidoya","year":"2010","unstructured":"Kidoya, H., Naito, H. & Takakura, N. Apelin induces enlarged and nonleaky blood vessels for functional recovery from ischemia. Blood 115, 3166\u20133174 (2010).","journal-title":"Blood"},{"key":"BFnm3040_CR32","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1161\/ATVBAHA.109.202028","volume":"30","author":"P Caruso","year":"2010","unstructured":"Caruso, P. et al. Dynamic changes in lung microRNA profiles during the development of pulmonary hypertension due to chronic hypoxia and monocrotaline. Arterioscler. Thromb. Vasc. Biol. 30, 716\u2013723 (2010).","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"BFnm3040_CR33","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1038\/leu.2009.246","volume":"24","author":"AR Forrest","year":"2010","unstructured":"Forrest, A.R. et al. Induction of microRNAs, mir-155, mir-222, mir-424 and mir-503, promotes monocytic differentiation through combinatorial regulation. Leukemia 24, 460\u2013466 (2010).","journal-title":"Leukemia"},{"key":"BFnm3040_CR34","doi-asserted-by":"publisher","first-page":"2138","DOI":"10.1091\/mbc.e10-01-0062","volume":"21","author":"S Sarkar","year":"2010","unstructured":"Sarkar, S., Dey, B.K. & Dutta, A. MiR-322\/424 and -503 are induced during muscle differentiation and promote cell cycle quiescence and differentiation by down-regulation of Cdc25A. Mol. Biol. Cell 21, 2138\u20132149 (2010).","journal-title":"Mol. Biol. Cell"},{"key":"BFnm3040_CR35","doi-asserted-by":"publisher","first-page":"4141","DOI":"10.1172\/JCI42980","volume":"120","author":"G Ghosh","year":"2010","unstructured":"Ghosh, G. et al. Hypoxia-induced microRNA-424 expression in human endothelial cells regulates HIF-alpha isoforms and promotes angiogenesis. J. Clin. Invest. 120, 4141\u20134154 (2010).","journal-title":"J. Clin. Invest."},{"key":"BFnm3040_CR36","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1165\/rcmb.2011-0416TE","volume":"46","author":"SA Comhair","year":"2012","unstructured":"Comhair, S.A. et al. Human primary lung endothelial cells in culture. Am. J. Respir. Cell Mol. Biol. 46, 723\u2013730 (2012).","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"BFnm3040_CR37","doi-asserted-by":"publisher","first-page":"L789","DOI":"10.1152\/ajplung.90306.2008","volume":"295","author":"M Aytekin","year":"2008","unstructured":"Aytekin, M. et al. High levels of hyaluronan in idiopathic pulmonary arterial hypertension. Am. J. Physiol. Lung Cell. Mol. Physiol. 295, L789\u2013L799 (2008).","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"BFnm3040_CR38","first-page":"3343","volume":"118","author":"HJ Chun","year":"2008","unstructured":"Chun, H.J. et al. Apelin signaling antagonizes Ang II effects in mouse models of atherosclerosis. J. Clin. Invest. 118, 3343\u20133354 (2008).","journal-title":"J. Clin. Invest."}],"container-title":["Nature Medicine"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/nm.3040.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nm.3040","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nm.3040.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T22:37:03Z","timestamp":1684449423000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/nm.3040"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,12,23]]},"references-count":38,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2013,1]]}},"alternative-id":["BFnm3040"],"URL":"https:\/\/doi.org\/10.1038\/nm.3040","relation":{},"ISSN":["1078-8956","1546-170X"],"issn-type":[{"value":"1078-8956","type":"print"},{"value":"1546-170X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,12,23]]}}}