{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T03:55:52Z","timestamp":1780372552251,"version":"3.54.1"},"reference-count":106,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T00:00:00Z","timestamp":1749168000000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008460","name":"National Center for Complementary and Integrative Health","doi-asserted-by":"publisher","award":["R00 AT010017"],"award-info":[{"award-number":["R00 AT010017"]}],"id":[{"id":"10.13039\/100008460","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Physiological Reports"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>People with Down syndrome (DS) have abnormal vascular physiology, demonstrated by low systolic blood pressure (BP) and low aortic stiffness that are accompanied by endothelial dysfunction. The TcMAC21 mouse model of DS has many features observed in people with DS, although vascular physiology has not been studied. At 4\u2009months old, male and female TcMAC21 mice exhibited lower systolic BP and aortic stiffness, as determined by aortic pulse wave velocity, which are accompanied by blunted carotid artery flow\u2010mediated vasodilation, indicating endothelial dysfunction, compared to euploid (i.e., control) mice. To determine a potential mechanism for blunted flow\u2010mediated vasodilation, we assessed endothelial glycocalyx properties, which mechanotransduces fluid shear stress to the endothelial cells, stimulating flow\u2010mediated vasodilation. We observed a lower glycocalyx thickness in the mesenteric microcirculation of TcMAC21 mice. Vascular abnormalities in TcMAC21 mice were accompanied by systemic inflammation. This is the first study to examine vascular physiology in the TcMAC21 mouse model of DS and investigate glycocalyx properties in any model of DS, including humans. Taken together, these findings support the use of the TcMAC21 mouse model to study the vascular physiology in people with DS and may provide translational insight into the role of glycocalyx in vascular abnormalities in DS.<\/jats:p>","DOI":"10.14814\/phy2.70384","type":"journal-article","created":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T04:26:51Z","timestamp":1749184011000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["<scp>TcMAC21<\/scp> mouse model recapitulates abnormal vascular physiology observed in humans with Down syndrome"],"prefix":"10.14814","volume":"13","author":[{"given":"Xiangyu","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Nutrition and Integrative Physiology Florida State University  Tallahassee Florida USA"},{"name":"Cardiology Division, Department of Medicine Emory University School of Medicine  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mostafa","family":"Sabouri","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Integrative Physiology Florida State University  Tallahassee Florida USA"},{"name":"Vascular Physiology Group, Department of Cell Biology and Physiology University of New Mexico School of Medicine  Albuquerque New Mexico USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan J.","family":"Irwin","sequence":"additional","affiliation":[{"name":"Department of Biological Science Florida State University  Tallahassee Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Bernardo","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Integrative Physiology Florida State University  Tallahassee Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2509-4686","authenticated-orcid":false,"given":"Daniel R.","family":"Machin","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Integrative Physiology Florida State University  Tallahassee Florida USA"},{"name":"Vascular Physiology Group, Department of Cell Biology and Physiology University of New Mexico School of Medicine  Albuquerque New Mexico USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,6]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0000000000003239"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.18-14-05456.1998"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3109\/07420528.2011.635231"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00544.2022"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10875\u2010011\u20109625\u20104"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00885.2020"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2004.04.047"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0735-1097(94)90141-4"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyae027"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2019.01.028"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2017011957"},{"key":"e_1_2_9_13_1","first-page":"117","article-title":"Segmental trisomy as a mouse model for down syndrome","volume":"384","author":"Davisson M. T.","year":"1993","journal-title":"Progress in Clinical and Biological Research"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2016.127"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2020.00670"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.122.059706"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12881-017-0475-7"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mvr.2013.08.007"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.118.312563"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10456-023-09880-x"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2015.3172"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.35706"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.2040-4603.2019.tb00074.x"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000249510.20326.72"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajh.2008.301"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000101744.47866.D5"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/1472-6823-5-6"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-014-2834-5"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.119.14240"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2020.06.013"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2003.09.016"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2023.02.012"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep39035"},{"key":"e_1_2_9_34_1","first-page":"448","article-title":"Leucocyte migration inhibition factor (LIF) production by lymphocytes of normal children, newborns, and children with immune deficiency","volume":"24","author":"Hahn T.","year":"1976","journal-title":"Clinical and Experimental Immunology"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.26.7.2119"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1999.277.2.H508"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-196705000-00005"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2019.154938"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI10842"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.56223"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-86585-5"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000048892.83521.58"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dhjo.2020.100947"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2019.00099"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01276.2010"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10439-011-0427-x"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.103322"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00104.2018"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.170120"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2019.04.011"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-023-00745-1"},{"key":"e_1_2_9_52_1","article-title":"Quantifying the mechanical properties of the endothelial glycocalyx with atomic force microscopy","volume":"72","author":"Marsh G.","year":"2013","journal-title":"Journal of Visualized Experiments"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.110.150896"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.03.021"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(98)00035-2"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1532-5415.1999.tb01291.x"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-31396-z"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.886655"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines9020221"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00490.2015"},{"key":"e_1_2_9_61_1","first-page":"220","volume-title":"Guide for the care and use of laboratory animals","author":"National Research Council (U.S.)","year":"2011"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00440.2007"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1093\/qjmed\/hcn024"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1111\/jar.12773"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2006.12.050"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2007.01.137"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2008.07.002"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiol.00035.2021"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00431.2024"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2013.06.013"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00297.2005"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004240000307"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.4093\/dmj.2014.38.6.464"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00092.2023"},{"key":"e_1_2_9_75_1","doi-asserted-by":"publisher","DOI":"10.2147\/VHRM.S21273"},{"key":"e_1_2_9_76_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2013.11.032"},{"key":"e_1_2_9_77_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-021-03520-w"},{"key":"e_1_2_9_78_1","doi-asserted-by":"publisher","DOI":"10.1111\/micc.12673"},{"key":"e_1_2_9_79_1","doi-asserted-by":"publisher","DOI":"10.1111\/jch.13930"},{"key":"e_1_2_9_80_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvad069"},{"key":"e_1_2_9_81_1","doi-asserted-by":"publisher","DOI":"10.17219\/acem\/68677"},{"key":"e_1_2_9_82_1","doi-asserted-by":"crossref","unstructured":"Sarver D. C. Xu C. Rodriguez S. Aja S. Jaffe A. E. Gao F. J. Delannoy M. Periasamy M. Kazuki Y. Oshimura M. Reeves R. H. &Wong G. W.(2023a).Hypermetabolism in mice carrying a near complete human chromosome 21.bioRxiv.https:\/\/doi.org\/10.7554\/elife.86023","DOI":"10.1101\/2023.01.30.526183"},{"key":"e_1_2_9_83_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.86023"},{"key":"e_1_2_9_84_1","doi-asserted-by":"publisher","DOI":"10.3109\/08916934.2015.1027815"},{"key":"e_1_2_9_85_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2016.05.034"},{"key":"e_1_2_9_86_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdr2.2301"},{"key":"e_1_2_9_87_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.93.6.1185"},{"key":"e_1_2_9_88_1","doi-asserted-by":"publisher","DOI":"10.1002\/wdev.230"},{"key":"e_1_2_9_89_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.81.3.772"},{"key":"e_1_2_9_90_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.114.04147"},{"key":"e_1_2_9_91_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40560-016-0182-z"},{"key":"e_1_2_9_92_1","first-page":"75","article-title":"Glycocalyx and endothelial (dys) function: From mice to men","volume":"58","author":"Berg B. M.","year":"2006","journal-title":"Pharmacological Reports"},{"key":"e_1_2_9_93_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000065917.53950.75"},{"key":"e_1_2_9_94_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41390-022-02321-3"},{"key":"e_1_2_9_95_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvsc.2015.04.011"},{"key":"e_1_2_9_96_1","first-page":"417","article-title":"Macrocytosis in down syndrome","volume":"95","author":"Wachtel T. J.","year":"1991","journal-title":"American Journal of Mental Retardation"},{"key":"e_1_2_9_97_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-39466-x"},{"key":"e_1_2_9_98_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.113.01744"},{"key":"e_1_2_9_99_1","first-page":"291","article-title":"Endothelial dysfunction and cardiovascular disease","volume":"2014","author":"Widmer R. J.","year":"2014","journal-title":"Global Cardiology Science and Practice"},{"key":"e_1_2_9_100_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.acra.2012.08.001"},{"key":"e_1_2_9_101_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bj.2020.08.007"},{"key":"e_1_2_9_102_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00162.2007"},{"key":"e_1_2_9_103_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2005.09.029"},{"key":"e_1_2_9_104_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00415.2022"},{"key":"e_1_2_9_105_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00656.2021"},{"key":"e_1_2_9_106_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2022.1090023"},{"key":"e_1_2_9_107_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2012.93"}],"container-title":["Physiological Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.14814\/phy2.70384","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T12:16:23Z","timestamp":1754914583000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.14814\/phy2.70384"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6]]},"references-count":106,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,6]]}},"alternative-id":["10.14814\/phy2.70384"],"URL":"https:\/\/doi.org\/10.14814\/phy2.70384","archive":["Portico"],"relation":{},"ISSN":["2051-817X","2051-817X"],"issn-type":[{"value":"2051-817X","type":"print"},{"value":"2051-817X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6]]},"assertion":[{"value":"2025-05-06","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":"2025-06-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70384"}}