{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T13:21:17Z","timestamp":1779888077577,"version":"3.53.1"},"reference-count":22,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2020,9,5]],"date-time":"2020-09-05T00:00:00Z","timestamp":1599264000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL113612"],"award-info":[{"award-number":["R01HL113612"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL133029"],"award-info":[{"award-number":["R01HL133029"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Microcirculation"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Treatment with BCR\u2010ABL tyrosine kinase inhibitors (TKIs) is the standard of care for patients with chronic myeloid leukemia, however evidence indicates these compounds may have cardiovascular side\u2010effects. This study sought to determine if ex vivo exposure of human adipose arterioles to the BCR\u2010ABL TKIs imatinib and nilotinib causes endothelial dysfunction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Human adipose arterioles were incubated overnight in cell culture media containing vehicle (PBS), imatinib (10\u00a0\u00b5mol\/L) or nilotinib (100\u00a0\u00b5mol\/L). Arterioles were cannulated onto glass pipettes and flow mediated dilation (FMD) was assessed via video microscopy. To determine the mechanism of vasodilation, FMD was re\u2010assessed in the presence of either the nitric oxide synthase inhibitor L\u2010NAME (100\u00a0\u00b5mol\/L) or the H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> scavenger PEG\u2010Catalase (500\u00a0U\/mL).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Neither imatinib nor nilotinib affected the magnitude of FMD (max dilation\u00a0=\u00a078\u00b117% vehicle, 80\u00a0\u00b1\u00a024% nilotinib, 73\u00a0\u00b1\u00a013% imatinib). FMD was decreased by L\u2010NAME in vehicle\u2010treated arterioles (max dilation\u00a0=\u00a047\u00b129%). Conversely, L\u2010NAME had no effect on FMD in imatinib\u2010 or nilotinib\u2010treated vessels (max dilation\u00a0=\u00a079\u00b114% and 80\u00a0\u00b1\u00a024%, respectively), rather FMD was inhibited by PEG\u2010Catalase (max dilation\u00a0=\u00a029\u00b111% and 29\u00a0\u00b1\u00a014%, respectively).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Incubating human arterioles with imatinib or nilotinib switches the mediator of FMD from vasoprotective nitric oxide to pro\u2010inflammatory H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/micc.12625","type":"journal-article","created":{"date-parts":[[2020,5,12]],"date-time":"2020-05-12T15:38:37Z","timestamp":1589297917000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["BCR\u2010ABL tyrosine kinase inhibitors promote pathological changes in dilator phenotype in the human microvasculature"],"prefix":"10.1111","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1416-1652","authenticated-orcid":false,"given":"Matthew J.","family":"Durand","sequence":"first","affiliation":[{"name":"Department of Physical Medicine and Rehabilitation Medical College of Wisconsin Milwaukee Wisconsin USA"},{"name":"Cardiovascular Center Medical College of Wisconsin Milwaukee Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shelby N.","family":"Hader","sequence":"additional","affiliation":[{"name":"Cardiovascular Center Medical College of Wisconsin Milwaukee Wisconsin USA"},{"name":"Department of Medicine Medical College of Wisconsin Milwaukee Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexa","family":"Derayunan","sequence":"additional","affiliation":[{"name":"Cardiovascular Center Medical College of Wisconsin Milwaukee Wisconsin USA"},{"name":"Department of Obstetrics and Gynecology Medical College of Wisconsin Milwaukee Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalya","family":"Zinkevich","sequence":"additional","affiliation":[{"name":"Cardiovascular Center Medical College of Wisconsin Milwaukee Wisconsin USA"},{"name":"Department of Medicine Medical College of Wisconsin Milwaukee Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0299-9589","authenticated-orcid":false,"given":"Jennifer J.","family":"McIntosh","sequence":"additional","affiliation":[{"name":"Cardiovascular Center Medical College of Wisconsin Milwaukee Wisconsin USA"},{"name":"Department of Obstetrics and Gynecology Medical College of Wisconsin Milwaukee Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9129-7492","authenticated-orcid":false,"given":"Andreas M.","family":"Beyer","sequence":"additional","affiliation":[{"name":"Cardiovascular Center Medical 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