{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T20:54:14Z","timestamp":1776027254442,"version":"3.50.1"},"reference-count":42,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2011,9,29]],"date-time":"2011-09-29T00:00:00Z","timestamp":1317254400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2012,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Cells from multiple origins contribute to vascular smooth muscle cell (VSMC) development. Phenotypic heterogeneity of VSMCs is associated with their point of developmental origin; however, the mechanisms driving such differences are unknown. We here examined the mechanisms controlling vascular bed\u2010specific differences in\n                    <jats:italic>Rgs5<\/jats:italic>\n                    expression during development.\n                    <jats:italic>Rgs5<\/jats:italic>\n                    levels were similar across different regions of the vasculature in neonatal animals but were &gt;15\u2010fold higher in descending aortas compared with carotid arteries of adult mice. Thus, vessel bed\u2010specific changes in regulation of\n                    <jats:italic>Rgs5<\/jats:italic>\n                    expression occurred during vessel maturation. Examination of adult\n                    <jats:italic>Rgs5<\/jats:italic>\n                    \u2010LacZ reporter mice revealed lower\n                    <jats:italic>Rgs5<\/jats:italic>\n                    expression in VSMCs originating from the third (carotid artery) branchial arch compared with those originating in the fourth and sixth (aortic B segment, right subclavian, and ductus arteriosus) branchial arches. Indeed, a mosaic\n                    <jats:italic>Rgs5<\/jats:italic>\n                    expression pattern, with discreet LacZ boundaries between VSMCs derived from different developmental origins, was observed. Furthermore,\n                    <jats:italic>Rgs5<\/jats:italic>\n                    \u2010LacZ expression was correlated with the site of VSMC origin (splanchic mesoderm \u2248 local mesenchyme &gt; somites &gt; proepicardium &gt; mesothelium). Surprisingly,\n                    <jats:italic>Rgs5<\/jats:italic>\n                    reporter activity in cultured carotid artery\u2010 and descending aorta\u2010derived cells did not recapitulate the differences observed\n                    <jats:italic>in vivo<\/jats:italic>\n                    . Consistent with a developmental origin\u2010specific epigenetic mechanism driving the observed expression differences\n                    <jats:italic>in vivo<\/jats:italic>\n                    , the\n                    <jats:italic>Rgs5<\/jats:italic>\n                    promoter showed increased methylation on CpG dinucleotides in carotid arteries compared with that in descending aortas in adult but not in neonatal mice.\n                    <jats:italic>In vitro<\/jats:italic>\n                    methylation of the\n                    <jats:italic>Rgs5<\/jats:italic>\n                    promoter confirmed that its activity is sensitive to transcriptional down\u2010regulation by CpG methylation. These data suggest that an origin\u2010dependent epigenetic program regulates vascular bed\u2010 and maturation state\u2010dependent regulation of VSMC\u2010specific gene transcription.\u2014Zhang, H., Gu, S., Al\u2010Sabeq, B., Wang, S., He, J., Tam, A., Cifelli, C., Mathalone, N., Tirgari, S., Boyd, S., Heximer, S. P. Origin\u2010specific epigenetic program correlates with vascular bedspecific differences in\n                    <jats:italic>Rgs5<\/jats:italic>\n                    expression.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    26, 181\u2013191 (2012).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.11-185454","type":"journal-article","created":{"date-parts":[[2011,9,30]],"date-time":"2011-09-30T07:18:30Z","timestamp":1317367110000},"page":"181-191","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Origin\u2010specific epigenetic program correlates with vascular bed\u2010specific differences in\n                    <i>Rgs5<\/i>\n                    expression"],"prefix":"10.1096","volume":"26","author":[{"given":"Hangjun","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Physiology, Heart, and Stroke University of Toronto  Toronto Ontario Canada"},{"name":"Richard Lewar Centre of Excellence in Cardiovascular Research  Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Physiology, Heart, and Stroke University of Toronto  Toronto Ontario Canada"},{"name":"Richard Lewar Centre of Excellence in Cardiovascular Research  Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Basil","family":"Al\u2010Sabeq","sequence":"additional","affiliation":[{"name":"Department of Physiology, Heart, and Stroke University of Toronto  Toronto Ontario Canada"},{"name":"Richard Lewar Centre of Excellence in Cardiovascular Research  Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sean","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Physiology, Heart, and Stroke University of Toronto  Toronto Ontario Canada"},{"name":"Richard Lewar Centre of Excellence in Cardiovascular Research  Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janet","family":"He","sequence":"additional","affiliation":[{"name":"Department of Physiology, Heart, and Stroke University of Toronto  Toronto Ontario Canada"},{"name":"Richard Lewar Centre of Excellence in Cardiovascular Research  Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alex","family":"Tam","sequence":"additional","affiliation":[{"name":"Department of Physiology, Heart, and Stroke University of Toronto  Toronto Ontario Canada"},{"name":"Richard Lewar Centre of Excellence in Cardiovascular Research  Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlo","family":"Cifelli","sequence":"additional","affiliation":[{"name":"Department of Physiology, Heart, and Stroke University of Toronto  Toronto Ontario Canada"},{"name":"Richard Lewar Centre of Excellence in Cardiovascular Research  Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nurit","family":"Mathalone","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Vision Sciences University of Toronto  Toronto Ontario Canada"},{"name":"Keenan Research Centre of the Li Ka Shing Knowledge Institute of St. Michael's Hospital  Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sam","family":"Tirgari","sequence":"additional","affiliation":[{"name":"Department of Physiology, Heart, and Stroke University of Toronto  Toronto Ontario Canada"},{"name":"Richard Lewar Centre of Excellence in Cardiovascular Research  Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shelley","family":"Boyd","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Vision Sciences University of Toronto  Toronto Ontario Canada"},{"name":"Keenan Research Centre of the Li Ka Shing Knowledge Institute of St. Michael's Hospital  Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott P.","family":"Heximer","sequence":"additional","affiliation":[{"name":"Department of Physiology, Heart, and Stroke University of Toronto  Toronto Ontario Canada"},{"name":"Richard Lewar Centre of Excellence in Cardiovascular Research  Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2011,9,29]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.107.141069"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ar.1092370312"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000227505.19472.69"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.127.8.1607"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1996.0229"},{"key":"e_1_2_5_7_1","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1159\/000159132","article-title":"Regional differences in platelet\u2010derived growth factor production by the canine aorta","volume":"33","author":"Madura J. 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