{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T05:24:34Z","timestamp":1785129874312,"version":"3.55.0"},"reference-count":43,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2016,4]]},"abstract":"<jats:sec>\n            <jats:title>Objective\u2014<\/jats:title>\n            <jats:p>\n              To determine the role of orai1 store\u2013operated Ca\n              <jats:sup>2+<\/jats:sup>\n              entry in foam cell formation and atherogenesis.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results\u2014<\/jats:title>\n            <jats:p>\n              Acute administration of oxidized low-density lipoprotein (oxLDL) activates an orai1-dependent Ca\n              <jats:sup>2+<\/jats:sup>\n              entry in macrophages. Chelation of intracellular Ca\n              <jats:sup>2+<\/jats:sup>\n              , inhibition of orai1 store\u2013operated Ca\n              <jats:sup>2+<\/jats:sup>\n              entry, or knockdown of orai1 dramatically inhibited oxLDL-induced upregulation of scavenger receptor A, uptake of modified LDL, and foam cell formation. Orai1-dependent Ca\n              <jats:sup>2+<\/jats:sup>\n              entry induces scavenger receptor A expression and foam cell formation through activation of calcineurin but not calmodulin kinase II. Activation of nuclear factor of activated T cells is not involved in calcineurin signaling to foam cell formation. However, oxLDL dephosohorylates and activates apoptosis signal\u2013regulating kinase 1 in macrophages. Orai1 knockdown prevents oxLDL-induced apoptosis signal\u2013regulating kinase 1 activation. Knockdown of apoptosis signal\u2013regulating kinase 1, or inhibition of its downstream effectors, JNK and p38 mitogen-activated protein kinase, reduces scavenger receptor A expression and foam cell formation. Notably, orai1 expression is increased in atherosclerotic plaques of apolipoprotein E\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice fed with high-cholesterol diet. Knockdown of orai1 with adenovirus harboring orai1 siRNA or inhibition of orai1 Ca\n              <jats:sup>2+<\/jats:sup>\n              entry with SKF96365 for 4 weeks dramatically inhibits atherosclerotic plaque development in high-cholesterol diet feeding apolipoprotein E\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice. In addition, inhibition of orai1 Ca\n              <jats:sup>2+<\/jats:sup>\n              entry prevents macrophage apoptosis in atherosclerotic plaque. Moreover, the expression of inflammatory genes in atherosclerotic lesions and the infiltration of myeloid cells into the aortic sinus plaques are decreased after blocking orai1 signaling.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>\n              Orai1-dependent Ca\n              <jats:sup>2+<\/jats:sup>\n              entry promotes atherogenesis possibly by promoting foam cell formation and vascular inflammation, rendering orai1 Ca\n              <jats:sup>2+<\/jats:sup>\n              channel a potential therapeutic target against atherosclerosis.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.116.307344","type":"journal-article","created":{"date-parts":[[2016,2,26]],"date-time":"2016-02-26T04:33:49Z","timestamp":1456461229000},"page":"618-628","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":75,"title":["Inhibition of Orai1 Store\u2013Operated Calcium Channel Prevents Foam Cell Formation and Atherosclerosis"],"prefix":"10.1161","volume":"36","author":[{"given":"Si-Jia","family":"Liang","sequence":"first","affiliation":[{"name":"From the Department of Pharmacology, Cardiac and Cerebrovascular Research Center (S.-J.L., D.-Y.Z., X.-Y.M., J.-Y.S., Q.-Q.W., J.-N.Y., B.-X.Y., F.-R.Z., Y.-Y.L., X.-F.L., J.L., J.-G.Z.) and Guangdong Province Key Laboratory of Brain Function and Disease (J.-G.Z.), Zhongshan School of Medicine, Division of Cardiac Surgery, The Key Laboratory of Assisted Circulation, Ministry of Health, The First Affiliated Hospital (J.-S.O.), and Department of Radiology, Intervention Radiology Institute, The Third..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"De-Yi","family":"Zeng","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, Cardiac and Cerebrovascular Research Center (S.-J.L., D.-Y.Z., X.-Y.M., J.-Y.S., Q.-Q.W., J.-N.Y., B.-X.Y., F.-R.Z., Y.-Y.L., X.-F.L., J.L., J.-G.Z.) and Guangdong Province Key Laboratory of Brain Function and Disease (J.-G.Z.), Zhongshan School of Medicine, Division of Cardiac Surgery, The Key Laboratory of Assisted Circulation, Ministry of Health, The First Affiliated Hospital (J.-S.O.), and Department of Radiology, Intervention Radiology Institute, The Third..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Yi","family":"Mai","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, Cardiac and Cerebrovascular Research Center (S.-J.L., D.-Y.Z., X.-Y.M., J.-Y.S., Q.-Q.W., J.-N.Y., B.-X.Y., F.-R.Z., Y.-Y.L., X.-F.L., J.L., J.-G.Z.) and Guangdong Province Key Laboratory of Brain Function and Disease (J.-G.Z.), Zhongshan School of Medicine, Division of Cardiac Surgery, The Key Laboratory of Assisted Circulation, Ministry of Health, The First Affiliated Hospital (J.-S.O.), and Department of Radiology, Intervention Radiology Institute, The Third..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Yan","family":"Shang","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, Cardiac and Cerebrovascular Research Center (S.-J.L., D.-Y.Z., X.-Y.M., J.-Y.S., Q.-Q.W., J.-N.Y., B.-X.Y., F.-R.Z., Y.-Y.L., X.-F.L., J.L., J.-G.Z.) and Guangdong Province Key Laboratory of Brain Function and Disease (J.-G.Z.), Zhongshan School of Medicine, Division of Cardiac Surgery, The Key Laboratory of Assisted Circulation, Ministry of Health, The First Affiliated Hospital (J.-S.O.), and Department of Radiology, Intervention Radiology Institute, The Third..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian-Qian","family":"Wu","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, Cardiac and Cerebrovascular Research Center (S.-J.L., D.-Y.Z., X.-Y.M., J.-Y.S., Q.-Q.W., J.-N.Y., B.-X.Y., F.-R.Z., Y.-Y.L., X.-F.L., J.L., J.-G.Z.) and Guangdong Province Key Laboratory of Brain Function and Disease (J.-G.Z.), Zhongshan School of Medicine, Division of Cardiac Surgery, The Key Laboratory of Assisted Circulation, Ministry of Health, The First Affiliated Hospital (J.-S.O.), and Department of Radiology, Intervention Radiology Institute, The Third..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Ni","family":"Yuan","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, Cardiac and Cerebrovascular Research Center (S.-J.L., D.-Y.Z., X.-Y.M., J.-Y.S., Q.-Q.W., J.-N.Y., B.-X.Y., F.-R.Z., Y.-Y.L., X.-F.L., J.L., J.-G.Z.) and Guangdong Province Key Laboratory of Brain Function and Disease (J.-G.Z.), Zhongshan School of Medicine, Division of Cardiac Surgery, The Key Laboratory of Assisted Circulation, Ministry of Health, The First Affiliated Hospital (J.-S.O.), and Department of Radiology, Intervention Radiology Institute, The Third..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bei-Xin","family":"Yu","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, Cardiac and Cerebrovascular Research Center (S.-J.L., D.-Y.Z., X.-Y.M., J.-Y.S., Q.-Q.W., J.-N.Y., B.-X.Y., F.-R.Z., Y.-Y.L., X.-F.L., J.L., J.-G.Z.) and Guangdong Province Key Laboratory of Brain Function and Disease (J.-G.Z.), Zhongshan School of Medicine, Division of Cardiac Surgery, The Key Laboratory of Assisted Circulation, Ministry of Health, The First Affiliated Hospital (J.-S.O.), and Department of Radiology, Intervention Radiology Institute, The Third..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Zhou","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, Cardiac and Cerebrovascular Research Center (S.-J.L., D.-Y.Z., X.-Y.M., J.-Y.S., Q.-Q.W., J.-N.Y., B.-X.Y., F.-R.Z., Y.-Y.L., X.-F.L., J.L., J.-G.Z.) and Guangdong Province Key Laboratory of Brain Function and Disease (J.-G.Z.), Zhongshan School of Medicine, Division of Cardiac Surgery, The Key Laboratory of Assisted Circulation, Ministry of Health, The First Affiliated Hospital (J.-S.O.), and Department of Radiology, Intervention Radiology Institute, The Third..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei-Ran","family":"Zhang","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, Cardiac and Cerebrovascular Research Center (S.-J.L., D.-Y.Z., X.-Y.M., J.-Y.S., Q.-Q.W., J.-N.Y., B.-X.Y., F.-R.Z., Y.-Y.L., X.-F.L., J.L., J.-G.Z.) and Guangdong Province Key Laboratory of Brain Function and Disease (J.-G.Z.), Zhongshan School of Medicine, Division of Cardiac Surgery, The Key Laboratory of Assisted Circulation, Ministry of Health, The First Affiliated Hospital (J.-S.O.), and Department of Radiology, Intervention Radiology Institute, The Third..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying-Ying","family":"Liu","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, Cardiac and Cerebrovascular Research Center (S.-J.L., D.-Y.Z., X.-Y.M., J.-Y.S., Q.-Q.W., J.-N.Y., B.-X.Y., F.-R.Z., Y.-Y.L., X.-F.L., J.L., J.-G.Z.) and Guangdong Province Key Laboratory of Brain Function and Disease (J.-G.Z.), Zhongshan School of Medicine, Division of Cardiac Surgery, The Key Laboratory of Assisted Circulation, Ministry of Health, The First Affiliated Hospital (J.-S.O.), and Department of Radiology, Intervention Radiology Institute, The Third..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Fei","family":"Lv","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, Cardiac and Cerebrovascular Research Center (S.-J.L., D.-Y.Z., X.-Y.M., J.-Y.S., Q.-Q.W., J.-N.Y., B.-X.Y., F.-R.Z., Y.-Y.L., X.-F.L., J.L., J.-G.Z.) and Guangdong Province Key Laboratory of Brain Function and Disease (J.-G.Z.), Zhongshan School of Medicine, Division of Cardiac Surgery, The Key Laboratory of Assisted Circulation, Ministry of Health, The First Affiliated Hospital (J.-S.O.), and Department of Radiology, Intervention Radiology Institute, The Third..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Liu","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, Cardiac and Cerebrovascular Research Center (S.-J.L., D.-Y.Z., X.-Y.M., J.-Y.S., Q.-Q.W., J.-N.Y., B.-X.Y., F.-R.Z., Y.-Y.L., X.-F.L., J.L., J.-G.Z.) and Guangdong Province Key Laboratory of Brain Function and Disease (J.-G.Z.), Zhongshan School of Medicine, Division of Cardiac Surgery, The Key Laboratory of Assisted Circulation, Ministry of Health, The First Affiliated Hospital (J.-S.O.), and Department of Radiology, Intervention Radiology Institute, The Third..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing-Song","family":"Ou","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, Cardiac and Cerebrovascular Research Center (S.-J.L., D.-Y.Z., X.-Y.M., J.-Y.S., Q.-Q.W., J.-N.Y., B.-X.Y., F.-R.Z., Y.-Y.L., X.-F.L., J.L., J.-G.Z.) and Guangdong Province Key Laboratory of Brain Function and Disease (J.-G.Z.), Zhongshan School of Medicine, Division of Cardiac Surgery, The Key Laboratory of Assisted Circulation, Ministry of Health, The First Affiliated Hospital (J.-S.O.), and Department of Radiology, Intervention Radiology Institute, The Third..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie-Sheng","family":"Qian","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, Cardiac and Cerebrovascular Research Center (S.-J.L., D.-Y.Z., X.-Y.M., J.-Y.S., Q.-Q.W., J.-N.Y., B.-X.Y., F.-R.Z., Y.-Y.L., X.-F.L., J.L., J.-G.Z.) and Guangdong Province Key Laboratory of Brain Function and Disease (J.-G.Z.), Zhongshan School of Medicine, Division of Cardiac Surgery, The Key Laboratory of Assisted Circulation, Ministry of Health, The First Affiliated Hospital (J.-S.O.), and Department of Radiology, Intervention Radiology Institute, The Third..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Guo","family":"Zhou","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, Cardiac and Cerebrovascular Research Center (S.-J.L., D.-Y.Z., X.-Y.M., J.-Y.S., Q.-Q.W., J.-N.Y., B.-X.Y., F.-R.Z., Y.-Y.L., X.-F.L., J.L., J.-G.Z.) and Guangdong Province Key Laboratory of Brain Function and Disease (J.-G.Z.), Zhongshan School of Medicine, Division of Cardiac Surgery, The Key Laboratory of Assisted Circulation, Ministry of Health, The First Affiliated Hospital (J.-S.O.), and Department of Radiology, Intervention Radiology Institute, The Third..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.111.074096"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.06.009"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2009.09.009"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pathol.1.110304.100100"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2012.02.015"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI13903"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2006.06.007"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1102-1235"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00029.2011"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2005.06.023"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.62.1.75"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.5551\/jat.12450"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.17.11.3013"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2004.10.028"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000154359.60886.33"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05637"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1997.77.4.901"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2005.05.055"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05122"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200502019"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1127883"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05108"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04147"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2009.00818.x"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0900082"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000338496.95579.56"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.108.124404"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI77483"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvt196"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-05-224659"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.111.246777"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2010.06.002"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1101909"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.275.5296.90"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.26.10.3785-3797.2006"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2009.00820.x"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2010.04.016"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00325.2009"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2011.05.015"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2010.09.011"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.278.5343.1638"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1500396"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2011.04.004"}],"container-title":["Arteriosclerosis, Thrombosis, and Vascular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/ATVBAHA.116.307344","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T23:07:13Z","timestamp":1715555233000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/ATVBAHA.116.307344"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,4]]},"references-count":43,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2016,4]]}},"alternative-id":["10.1161\/ATVBAHA.116.307344"],"URL":"https:\/\/doi.org\/10.1161\/atvbaha.116.307344","relation":{},"ISSN":["1079-5642","1524-4636"],"issn-type":[{"value":"1079-5642","type":"print"},{"value":"1524-4636","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,4]]},"assertion":[{"value":"2016-01-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-02-14","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-02-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}