{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T14:15:14Z","timestamp":1791728114023,"version":"4.3.4"},"reference-count":38,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"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":[[2025,7]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>Diabetes is characterized by chronic hyperglycemia that leads to systemic vascular complications. Hyperglycemia impairs endothelial function and promotes vascular inflammation, resulting in leukocytosis, altered hematopoiesis, and cardiovascular complications. Bone marrow endothelial cells play a pivotal role in regulating myeloid progenitor cells and leukocyte trafficking. However, the effects of diabetes on the structure and function of bone marrow vasculature remain poorly understood. To address this, we used a multiscale imaging approach integrating intravital microscopy, dynamic contrast-enhanced magnetic resonance imaging, and multispectral optoacoustic tomography to investigate diabetes-induced vascular changes in the bone marrow.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>Diabetes was induced in C57BL\/6J female mice using streptozotocin. Flow cytometry and histology characterized bone marrow myeloid progenitors, blood leukocytes, and bone marrow endothelial cell populations, as well as hypoxia. Intravital microscopy was used to visualize vascular density, permeability, and sprouting angiogenesis in the calvarial marrow. Dynamic contrast-enhanced magnetic resonance imaging quantified vascular density and permeability in the femoral marrow, while multispectral optoacoustic tomography assessed hemoglobin oxygenation in the calvarial marrow.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>\n              Hyperglycemia significantly increased myelopoiesis, leading to elevated leukocytosis driving diabetic inflammation. Flow cytometry and histology revealed increased bone marrow endothelial cell numbers (\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              =0.0006), while intravital microscopy showed elevated vascular permeability (\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              =0.0095) and sprouting angiogenesis (\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              =0.0095). Dynamic contrast-enhanced magnetic resonance imaging confirmed greater vascular density (\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              =0.019) and leakiness (\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              =0.0062), and multispectral optoacoustic tomography detected reduced hemoglobin oxygenation and increased hypoxia in the diabetic marrow (\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              =0.0065), reflecting a hypoxic niche favorable to hematopoietic stem and progenitor cells. This likely drives angiogenesis and contributes to inflammatory hematopoiesis in diabetes.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>This study demonstrates that diabetes induces profound vascular remodeling and hypoxia in the bone marrow, reshaping the hematopoietic niche and driving myelopoiesis and leukocytosis. By validating dynamic contrast-enhanced magnetic resonance imaging and multispectral optoacoustic tomography as noninvasive translational tools, coupled with intravital microscopy, we provide a comprehensive framework for exploring novel therapies targeting bone marrow vasculature to mitigate inflammation-driven outcomes in diabetes.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.124.322358","type":"journal-article","created":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T09:00:35Z","timestamp":1749114035000},"page":"1192-1206","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":6,"title":["Visualizing Vascular Bone Marrow Niche Alterations in Diabetes"],"prefix":"10.1161","volume":"45","author":[{"given":"Narmeen","family":"Haj","sequence":"first","affiliation":[{"name":"Faculty of Biomedical Engineering (N.H., A.T., M.B., N.K., S.N., S.K.-A., K.V.), Technion-Israel Institute of Technology, Haifa."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8520-1829","authenticated-orcid":true,"given":"Ashish","family":"Tiwari","sequence":"additional","affiliation":[{"name":"Faculty of Biomedical Engineering (N.H., A.T., M.B., N.K., S.N., S.K.-A., K.V.), Technion-Israel Institute of Technology, Haifa."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1996-9272","authenticated-orcid":true,"given":"Maria","family":"Berihu","sequence":"additional","affiliation":[{"name":"Faculty of Biomedical Engineering (N.H., A.T., M.B., N.K., S.N., S.K.-A., K.V.), Technion-Israel Institute of Technology, Haifa."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nedaa","family":"Kher","sequence":"additional","affiliation":[{"name":"Faculty of Biomedical Engineering (N.H., A.T., M.B., N.K., S.N., S.K.-A., K.V.), Technion-Israel Institute of Technology, Haifa."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siraj","family":"Nsraldeen","sequence":"additional","affiliation":[{"name":"Faculty of Biomedical Engineering (N.H., A.T., M.B., N.K., S.N., S.K.-A., K.V.), Technion-Israel Institute of Technology, Haifa."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3342-355X","authenticated-orcid":true,"given":"Maya","family":"Holdengreber","sequence":"additional","affiliation":[{"name":"Biomedical Core Facility, Rappaport Faculty of Medicine (M.H., G.S.), Technion-Israel Institute of Technology, Haifa."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiri","family":"Karni-Ashkenazi","sequence":"additional","affiliation":[{"name":"Faculty of Biomedical Engineering (N.H., A.T., M.B., N.K., S.N., S.K.-A., K.V.), Technion-Israel Institute of Technology, Haifa."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5278-5522","authenticated-orcid":true,"given":"Bin","family":"Zhou","sequence":"additional","affiliation":[{"name":"New Cornerstone Science Laboratory, State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, China (B.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Galit","family":"Saar","sequence":"additional","affiliation":[{"name":"Biomedical Core Facility, Rappaport Faculty of Medicine (M.H., G.S.), Technion-Israel Institute of Technology, Haifa."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8888-627X","authenticated-orcid":true,"given":"Daniel J.","family":"Stuckey","sequence":"additional","affiliation":[{"name":"Centre for Advanced Biomedical Imaging, University College London, United Kingdom (D.J.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrien","family":"Vandoorne","sequence":"additional","affiliation":[{"name":"Faculty of Biomedical Engineering (N.H., A.T., M.B., N.K., S.N., S.K.-A., K.V.), Technion-Israel Institute of Technology, Haifa."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-023-00985-4"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2015.19"},{"key":"e_1_3_3_4_2","first-page":"853","article-title":"Endothelial dysfunction in diabetes mellitus.","volume":"3","author":"Hadi HAR","year":"2007","unstructured":"Hadi HAR, Suwaidi JA. Endothelial dysfunction in diabetes mellitus. Vasc Health Risk Manag. 2007;3:853\u2013876.","journal-title":"Vasc Health Risk Manag"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01400-z"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2021.12.013"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(99)01046-6"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)68967-8"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.2337\/db19-0080"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.11-7784"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.120.046038"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0064-0"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature16943"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10783"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature17624"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.118.313302"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/s44161-021-00002-8"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.3c11201"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.109.200154"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2015.125"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms7020"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/lsa.2016.201"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pacs.2019.01.003"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2013.04.001"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2014.03.029"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2019-00980"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/918267"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2024.1359255"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11154-015-9310-7"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10144"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.118.11782"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000091257.27563.32"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.112.093245"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2016.04.016"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2730"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1039\/c6cs00765a"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10456-010-9170-4"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.00098"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2021.754369"}],"container-title":["Arteriosclerosis, Thrombosis, and Vascular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/ATVBAHA.124.322358","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T18:01:07Z","timestamp":1750874467000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/ATVBAHA.124.322358"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7]]},"references-count":38,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2025,7]]}},"alternative-id":["10.1161\/ATVBAHA.124.322358"],"URL":"https:\/\/doi.org\/10.1161\/atvbaha.124.322358","relation":{},"ISSN":["1079-5642","1524-4636"],"issn-type":[{"value":"1079-5642","type":"print"},{"value":"1524-4636","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7]]},"assertion":[{"value":"2024-12-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}