{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:54:56Z","timestamp":1787018096001,"version":"build-2736575974"},"reference-count":60,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2017,4,5]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Monocrotaline has been widely used to establish an animal model of pulmonary hypertension. The molecular target underlying monocrotaline\u2010induced pulmonary artery endothelial injury and pulmonary hypertension remains unknown. The extracellular calcium\u2013sensing receptor (CaSR) and particularly its extracellular domain hold the potential structural basis for monocrotaline to bind. This study aimed to reveal whether monocrotaline induces pulmonary hypertension by targeting the CaSR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Nuclear magnetic resonance screening through Water\n                      <jats:styled-content style=\"fixed-case\">LOGSY<\/jats:styled-content>\n                      (water ligand\u2010observed gradient spectroscopy) and saturation transfer difference on protein preparation demonstrated the binding of monocrotaline to the CaSR. Immunocytochemical staining showed colocalization of monocrotaline with the CaSR in cultured pulmonary artery endothelial cells. Cellular thermal shift assay further verified the binding of monocrotaline to the CaSR in pulmonary arteries from monocrotaline\u2010injected rats. Monocrotaline enhanced the assembly of CaSR, triggered the mobilization of calcium signaling, and damaged pulmonary artery endothelial cells in a CaSR\u2010dependent manner. Finally, monocrotaline\u2010induced pulmonary hypertension in rats was significantly attenuated or abolished by the inhibitor, the general or lung knockdown or knockout of CaSR.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">Monocrotaline aggregates on and activates the CaSR of pulmonary artery endothelial cells to trigger endothelial damage and, ultimately, induces pulmonary hypertension.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.116.004865","type":"journal-article","created":{"date-parts":[[2017,3,22]],"date-time":"2017-03-22T20:32:10Z","timestamp":1490214730000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":52,"title":["Monocrotaline Induces Endothelial Injury and Pulmonary Hypertension by Targeting the Extracellular Calcium\u2013Sensing Receptor"],"prefix":"10.1161","volume":"6","author":[{"given":"Rui","family":"Xiao","sequence":"first","affiliation":[{"name":"Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, China"},{"name":"Key Laboratory of Pulmonary Diseases of Ministry of Health, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Su","sequence":"additional","affiliation":[{"name":"Key Laboratory of Pulmonary Diseases of Ministry of Health, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, China"},{"name":"Department of Respiratory Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, China"},{"name":"Key Laboratory of Pulmonary Diseases of Ministry of Health, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengxiang","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, China"},{"name":"Key Laboratory of Pulmonary Diseases of Ministry of Health, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingxun","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, China"},{"name":"Key Laboratory of Pulmonary Diseases of Ministry of Health, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiwei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Pulmonary Diseases of Ministry of Health, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, China"},{"name":"Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yankai","family":"Lu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Pulmonary Diseases of Ministry of Health, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, China"},{"name":"Department of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiansha","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Pulmonary Diseases of Ministry of Health, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, China"},{"name":"Department of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Pulmonary Diseases of Ministry of Health, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, China"},{"name":"Department of Respiratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, China"},{"name":"Key Laboratory of Pulmonary Diseases of Ministry of Health, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinghua","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, China"},{"name":"Key Laboratory of Pulmonary Diseases of Ministry of Health, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, China"},{"name":"Key Laboratory of Molecular Biophysics of the Ministry of Education, Huazhong University of Science and Technology (HUST), Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_5_2_2","first-page":"744","article-title":"Pulmonary arteritis produced in rat by feeding Crotalaria spectabilis","volume":"10","author":"Lalich JJ","year":"1961","unstructured":"Lalich JJ, Merkow L. Pulmonary arteritis produced in rat by feeding Crotalaria spectabilis. Lab Invest. 1961;10:744\u2013750.","journal-title":"Lab Invest"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1136\/thx.22.2.176"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI77656"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3877"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00212.2011"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pupt.2015.09.007"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-38664-0_5"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2011.4168"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.112.266361"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00050.2016"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1021\/tx960173v"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M001372200"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.200402022"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-4274(83)90002-4"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2013.145"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1021\/tx5002139"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tetlet.2014.05.055"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2016.01.007"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.417154"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep15286"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(01)75886-9"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1523918113"},{"key":"e_1_3_5_24_2","first-page":"12","article-title":"Generation of multi\u2010gene knockout rabbits using the Cas9\/gRNA system","volume":"3","author":"Yan Q","year":"2014","unstructured":"Yan Q, Zhang Q, Yang H, Zou Q, Tang C, Fan N, Lai L. Generation of multi\u2010gene knockout rabbits using the Cas9\/gRNA system. Cell Regen (Lond). 2014;3:12.","journal-title":"Cell Regen (Lond)"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.1212"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.137.9.8756555"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2013.02.009"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1231143"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2647"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.08.021"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0b013e328340a0e4"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2014.02.022"},{"key":"e_1_3_5_33_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00864.2014"},{"key":"e_1_3_5_34_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.114.008750"},{"key":"e_1_3_5_35_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.113.004136"},{"key":"e_1_3_5_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vph.2010.09.002"},{"key":"e_1_3_5_37_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200707-1083OC"},{"key":"e_1_3_5_38_2","doi-asserted-by":"publisher","DOI":"10.1113\/EP085182"},{"key":"e_1_3_5_39_2","unstructured":"\u201cDimethylformamide\u201d. Spectral database for organic compounds. Japan: AIST. Accessed June 28 2012."},{"key":"e_1_3_5_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2006.01.135"},{"key":"e_1_3_5_41_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1233606"},{"key":"e_1_3_5_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2014.138"},{"key":"e_1_3_5_43_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-94-007-2888-2_5"},{"key":"e_1_3_5_44_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00315.2009"},{"key":"e_1_3_5_45_2","doi-asserted-by":"publisher","DOI":"10.1378\/chest.124.6.2093"},{"key":"e_1_3_5_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2015.02.049"},{"key":"e_1_3_5_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1357-2725(97)00010-1"},{"key":"e_1_3_5_48_2","doi-asserted-by":"publisher","DOI":"10.1006\/taap.1998.8398"},{"key":"e_1_3_5_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxicon.2011.04.010"},{"key":"e_1_3_5_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2011.07.063"},{"key":"e_1_3_5_51_2","volume-title":"Chemistry and Toxicology of Pyrrolizidine Alkaloids","author":"Mattocks AR","year":"1986","unstructured":"Mattocks AR. Chemistry and Toxicology of Pyrrolizidine Alkaloids. London: London Academic Press; 1986."},{"key":"e_1_3_5_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/0041-0101(89)90117-7"},{"key":"e_1_3_5_53_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/26.23.5441"},{"key":"e_1_3_5_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vph.2007.01.005"},{"key":"e_1_3_5_55_2","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.2012.069104"},{"key":"e_1_3_5_56_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2002-220240"},{"key":"e_1_3_5_57_2","doi-asserted-by":"publisher","DOI":"10.1159\/000369627"},{"key":"e_1_3_5_58_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M400724200"},{"key":"e_1_3_5_59_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.06-6304fje"},{"key":"e_1_3_5_60_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00529.2009"},{"key":"e_1_3_5_61_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.493.65.2"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.116.004865","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T06:22:20Z","timestamp":1715581340000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.116.004865"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,4,5]]},"references-count":60,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2017,4,5]]}},"alternative-id":["10.1161\/JAHA.116.004865"],"URL":"https:\/\/doi.org\/10.1161\/jaha.116.004865","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,4,5]]},"assertion":[{"value":"2016-10-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-01-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-03-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e004865"}}