{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:53:46Z","timestamp":1787018026715,"version":"build-2736575974"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","license":[{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Low wall shear stress (WSS) at arterial bifurcations and curves damages endothelial cells, promoting the development of atherosclerosis. Although the accumulation of iron in plaques has been observed, the mechanisms behind it and its effects are not fully understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>\n                      Detect the iron content in different parts of the mouse partial carotid artery ligation model and the aorta. The chelating iron therapy was used to assess the impact of low WSS\u2013induced iron accumulation and atherosclerosis in the arterial wall. In vitro experiments utilized human umbilical vein endothelial cells and an orbital-shaker model to simulate WSS. Mice with endothelial cell\u2013specific knockout of IRP2 (iron regulatory protein 2) and deletion of Apoe (Apolipoprotein e;\n                      <jats:italic toggle=\"yes\">Apoe<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic toggle=\"yes\">\u2212\/\u2212<\/jats:italic>\n                      <\/jats:sup>\n                      <jats:italic toggle=\"yes\">IRP2<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic toggle=\"yes\">iEcko<\/jats:italic>\n                      <\/jats:sup>\n                      ) were constructed, as well as a human umbilical vein endothelial cell line with\n                      <jats:italic toggle=\"yes\">IRP2<\/jats:italic>\n                      knockdown.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      We investigated the iron accumulation induced by low WSS in carotid arteries. Hinokitiol, an iron chelator, was found to reduce this iron buildup and decrease the progression of atherosclerosis. Low WSS in the carotid arteries led to chronic iron accumulation, which altered the expression of iron metabolism\u2013related proteins in endothelial cells, particularly IRP2. Knocking down\n                      <jats:italic toggle=\"yes\">IRP2<\/jats:italic>\n                      in endothelial cells resulted in an increase in the expression of inflammation-related proteins and a significant elevation in the expression of HIFs (hypoxia-inducible factors).\n                      <jats:italic toggle=\"yes\">Apoe<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic toggle=\"yes\">\u2212\/\u2212<\/jats:italic>\n                      <\/jats:sup>\n                      <jats:italic toggle=\"yes\">IRP2<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic toggle=\"yes\">iEcko<\/jats:italic>\n                      <\/jats:sup>\n                      mice exhibited an increased susceptibility to atherosclerosis. The use of HIF inhibitors, PX-478 and PT-2385, was able to suppress the exacerbation of atherosclerosis in\n                      <jats:italic toggle=\"yes\">Apoe<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic toggle=\"yes\">\u2212\/\u2212<\/jats:italic>\n                      <\/jats:sup>\n                      mice caused by the endothelial cell\u2013specific knockout of\n                      <jats:italic toggle=\"yes\">IRP2<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>Our results indicate that low WSS\u2013induced endothelial cell iron metabolism abnormalities, by inducing arterial wall iron accumulation and abnormal expression of iron metabolism\u2013related proteins, promote the occurrence and development of atherosclerosis. The use of iron chelators can alleviate the onset and progression of low WSS\u2013induced atherosclerosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/atvbaha.125.322495","type":"journal-article","created":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T09:00:18Z","timestamp":1759395618000},"page":"1983-1996","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Low Wall Shear Stress Promotes Atheroma via Arterial Iron Accumulation"],"prefix":"10.1161","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8342-5236","authenticated-orcid":true,"given":"Lei","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Vascular Surgery (L.Z., Z.Z., Y.L., B.Z., Z.C., J.C., T.Q.), Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, China."},{"name":"Department of Vascular Surgery, General Surgery, Qilu Hospital of Shandong University, Jinan, China (L.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1696-5259","authenticated-orcid":true,"given":"Zhenxi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery (L.Z., Z.Z., Y.L., B.Z., Z.C., J.C., T.Q.), Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery (L.Z., Z.Z., Y.L., B.Z., Z.C., J.C., T.Q.), Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4316-2187","authenticated-orcid":true,"given":"Chen","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Pathology (C.C.), Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4309-5697","authenticated-orcid":true,"given":"Biao","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery (L.Z., Z.Z., Y.L., B.Z., Z.C., J.C., T.Q.), Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4822-1083","authenticated-orcid":true,"given":"Run","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery and Intervention, The Affiliated Suzhou Hospital of Nanjing Medical University, China (R.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhipeng","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery (L.Z., Z.Z., Y.L., B.Z., Z.C., J.C., T.Q.), Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7421-1512","authenticated-orcid":true,"given":"Liu","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, China (L.Y., K.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery (L.Z., Z.Z., Y.L., B.Z., Z.C., J.C., T.Q.), Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9738-049X","authenticated-orcid":true,"given":"Kuanyu","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, China (L.Y., K.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2695-2555","authenticated-orcid":true,"given":"Tong","family":"Qiao","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery (L.Z., Z.Z., Y.L., B.Z., Z.C., J.C., T.Q.), Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.04.004"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-023-00883-1"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-022-00735-4"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.3724\/abbs.2022196"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-023-00928-2"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(81)92463-6"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2020.8167"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13578-020-00500-5"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.7554\/elife.80494"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-023-00648-1"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2321929121"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.3791\/54632"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1820051116"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.3390\/antiox13091036"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-23175-y"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202301852"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2008.12.004"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00004-09"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2012.05.010"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI7664"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.112.246108"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.116.307830"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.06.028"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1176326"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1176333"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2020.02.011"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2021.101156"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-024-05740-4"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehz112"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.123.324082"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI93025"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2121400119"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aah3862"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2021.06.016"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2024.176340"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2022.08.011"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2023.0150"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13578-023-01044-0"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2020.07.026"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvae270"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-020-0227-y"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/84859"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-04-1365"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.3390\/genes12091365"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2121-11-66"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1177\/0003319716662423"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI137557"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI57322"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.123.324054"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-11-122648"}],"container-title":["Arteriosclerosis, Thrombosis, and Vascular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/ATVBAHA.125.322495","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T15:45:37Z","timestamp":1767714337000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/ATVBAHA.125.322495"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11]]},"references-count":50,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1161\/ATVBAHA.125.322495"],"URL":"https:\/\/doi.org\/10.1161\/atvbaha.125.322495","relation":{},"ISSN":["1079-5642","1524-4636"],"issn-type":[{"value":"1079-5642","type":"print"},{"value":"1524-4636","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11]]},"assertion":[{"value":"2025-01-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-10","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}