{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T22:10:34Z","timestamp":1793139034170,"version":"4.5.0"},"reference-count":116,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:p>Kinase inhibitors (KIs) targeting oncogenic molecular pathways have revolutionized cancer therapy. By directly targeting specific tumor-driving kinases, targeted therapies have fewer side effects compared with chemotherapy. Despite the enhanced specificity, cardiovascular side effects have emerged with many targeted cancer therapies that limit long-term outcomes in patients with cancer. Endothelial cells lining all blood vessels are critical to cardiovascular health and are also exposed to circulating levels of systemic anticancer therapies. Both on- and off-target perturbation of signaling pathways from KIs can cause endothelial dysfunction, resulting in cardiovascular toxicity. As such, the endothelium is a potential source, and also a therapeutic target for prevention, of cardiovascular toxicity. In this review, we examine the evidence for KI-induced endothelial cell dysfunction as a mechanism for the cardiovascular toxicities of vascular endothelial growth factor inhibitors, BCR-Abl (breakpoint cluster region-Abelson proto-oncogene) KIs, Bruton tyrosine inhibitors, and emerging information regarding endothelial toxicity of newer classes of KIs.<\/jats:p>","DOI":"10.1161\/atvbaha.124.319864","type":"journal-article","created":{"date-parts":[[2024,8,15]],"date-time":"2024-08-15T09:00:58Z","timestamp":1723712458000},"page":"2143-2153","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":18,"title":["Endothelium as a Source of Cardiovascular Toxicity From Antitumor Kinase Inhibitors"],"prefix":"10.1161","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6839-4996","authenticated-orcid":true,"given":"Richard J.","family":"Travers","sequence":"first","affiliation":[{"name":"Molecular Cardiology Research Institute (R.J.T., A.S., I.Z.J.), Tufts Medical Center, Boston, MA."},{"name":"Division of Hematology and Oncology (R.J.T.), Tufts Medical Center, Boston, MA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4719-5792","authenticated-orcid":true,"given":"Alec","family":"Stepanian","sequence":"additional","affiliation":[{"name":"Molecular Cardiology Research Institute (R.J.T., A.S., I.Z.J.), Tufts Medical Center, Boston, MA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9300-1253","authenticated-orcid":true,"given":"Iris Z.","family":"Jaffe","sequence":"additional","affiliation":[{"name":"Molecular Cardiology Research Institute (R.J.T., A.S., I.Z.J.), Tufts Medical Center, Boston, MA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.115.020406"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-021-00252-y"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-020-0347-2"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1517\/14740338.2012.672971"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1042\/CS20160246"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1177\/1358863X20914978"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2022.108116"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2016.08.006"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2015.36"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-011-0729-7"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-09-739086"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(18)30176-5"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clml.2012.04.005"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2015.5932"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2018.188987"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00279-2020"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.03957-2020"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mayocp.2020.11.005"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2021.758010"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2019000034"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2014.11.009"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines9070781"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0294438"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-10-881557"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1177\/1076029614550817"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00323.2014"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2008.00492.x"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1080\/10428194.2016.1239258"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2020.117275"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1179\/joc.2006.18.1.56"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2018020396"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.v122.21.257.257"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1111\/micc.12625"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.309491"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI86249"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0039-1688787"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2017.245"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2007.01.024"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1080\/03007995.2017.1399870"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.24174"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2015.05.025"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01096-2017"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.1019"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-0667"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2018.00537"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00031.2015"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6603923"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2009.52"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41698-018-0056-z"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-022-00838-y"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1002\/bit.26297"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines9111630"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1111\/cas.13536"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.11813"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40261-018-0709-2"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchf.2012.09.001"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cjca.2014.02.011"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2010.34.4309"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.echo.2018.09.019"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11912-022-01224-0"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1007\/5584_2016_90"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.115.305364"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.30344"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2021.115420"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2012.136"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10456-012-9327-4"},{"key":"e_1_3_3_68_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.111.182220"},{"key":"e_1_3_3_69_2","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0000000000000662"},{"key":"e_1_3_3_70_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.109.149690"},{"key":"e_1_3_3_71_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.122.19079"},{"key":"e_1_3_3_72_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvz260"},{"key":"e_1_3_3_73_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2023.116007"},{"key":"e_1_3_3_74_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jash.2012.06.003"},{"key":"e_1_3_3_75_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvz021"},{"key":"e_1_3_3_76_2","doi-asserted-by":"publisher","DOI":"10.1080\/20013078.2019.1629865"},{"key":"e_1_3_3_77_2","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics11040640"},{"key":"e_1_3_3_78_2","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfv410"},{"key":"e_1_3_3_79_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.90972.2008"},{"key":"e_1_3_3_80_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C300012200"},{"key":"e_1_3_3_81_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.108.776831"},{"key":"e_1_3_3_82_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.115.307778"},{"key":"e_1_3_3_83_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2018.00382"},{"key":"e_1_3_3_84_2","doi-asserted-by":"publisher","DOI":"10.1042\/CS20210059"},{"key":"e_1_3_3_85_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2022.166352"},{"key":"e_1_3_3_86_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00172.2015"},{"key":"e_1_3_3_87_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-019-0798-2"},{"key":"e_1_3_3_88_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2012.01.022"},{"key":"e_1_3_3_89_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3005066"},{"key":"e_1_3_3_90_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3702"},{"key":"e_1_3_3_91_2","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2017.171041"},{"key":"e_1_3_3_92_2","doi-asserted-by":"publisher","DOI":"10.1136\/openhrt-2019-001049"},{"key":"e_1_3_3_93_2","doi-asserted-by":"publisher","DOI":"10.1136\/heartjnl-2021-319110"},{"key":"e_1_3_3_94_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2012.04.063"},{"key":"e_1_3_3_95_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2015.2"},{"key":"e_1_3_3_96_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.120.049210"},{"key":"e_1_3_3_97_2","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics14091876"},{"key":"e_1_3_3_98_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-022-01302-7"},{"key":"e_1_3_3_99_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.625498"},{"key":"e_1_3_3_100_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12882-022-02873-w"},{"key":"e_1_3_3_101_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaf2584"},{"key":"e_1_3_3_102_2","doi-asserted-by":"publisher","DOI":"10.1111\/ejh.13590"},{"key":"e_1_3_3_103_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.123.029361"},{"key":"e_1_3_3_104_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1904059"},{"key":"e_1_3_3_105_2","doi-asserted-by":"publisher","DOI":"10.1177\/17588359211019675"},{"key":"e_1_3_3_106_2","doi-asserted-by":"publisher","DOI":"10.21037\/jtd.2019.09.15"},{"key":"e_1_3_3_107_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaccao.2022.09.006"},{"key":"e_1_3_3_108_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.5393"},{"key":"e_1_3_3_109_2","doi-asserted-by":"publisher","DOI":"10.4065\/83.6.679"},{"key":"e_1_3_3_110_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15061908"},{"key":"e_1_3_3_111_2","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.03271-2020"},{"key":"e_1_3_3_112_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1358"},{"key":"e_1_3_3_113_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2017"},{"key":"e_1_3_3_114_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1624566"},{"key":"e_1_3_3_115_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aan4368"},{"key":"e_1_3_3_116_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.hlc.2023.11.003"},{"key":"e_1_3_3_117_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00467.2019"}],"container-title":["Arteriosclerosis, Thrombosis, and Vascular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/ATVBAHA.124.319864","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T19:11:18Z","timestamp":1748545878000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/ATVBAHA.124.319864"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10]]},"references-count":116,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2024,10]]}},"alternative-id":["10.1161\/ATVBAHA.124.319864"],"URL":"https:\/\/doi.org\/10.1161\/atvbaha.124.319864","relation":{},"ISSN":["1079-5642","1524-4636"],"issn-type":[{"value":"1079-5642","type":"print"},{"value":"1524-4636","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10]]},"assertion":[{"value":"2024-08-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}