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Our aim was to determine the effect of moderate alcohol (EtOH) exposure on the expansion and differentiation of S100 calcium\u2010binding protein B positive (S100\u03b2<jats:sup>+<\/jats:sup>) resident vascular stem cells and their contribution to pathologic vessel remodeling in a mouse model of arteriosclerosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and Results<\/jats:title><jats:p>Lineage tracing analysis of S100\u03b2<jats:sup>+<\/jats:sup> cells was performed in male and female S100\u03b2\u2010eGFP\/Cre\/ERT2\u2013dTomato transgenic mice treated daily with or without EtOH by oral gavage (peak BAC: 15\u00a0mM or 0.07%) following left common carotid artery ligation for 14\u00a0days. Carotid arteries (ligated or sham\u2010operated) were harvested for morphological analysis and confocal assessment of fluorescent\u2010tagged S100 \u03b2 <jats:sup>+<\/jats:sup> cells in FFPE carotid cross sections.<\/jats:p><jats:p>Ligation\u2010induced carotid remodeling was more robust in males than in females. EtOH\u2010gavaged mice had less adventitial thickening and markedly reduced neointimal formation compared to controls, with a more pronounced inhibitory effect in males compared to females. There was significant expansion of S100\u03b2<jats:sup>+<\/jats:sup>\u2010marked cells in vessels postligation, primarily in the neointimal compartment. EtOH treatment reduced the fraction of S100\u03b2<jats:sup>+<\/jats:sup> cells in carotid cross sections, concomitant with attenuated remodeling. In vitro, EtOH attenuated Sonic Hedgehog\u2010stimulated myogenic differentiation (as evidenced by reduced calponin and myosin heavy chain expression) of isolated murine S100\u03b2<jats:sup>+<\/jats:sup> vascular stem cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These data highlight resident vascular S100\u03b2<jats:sup>+<\/jats:sup> stem cells as a novel target population for alcohol and suggest that regulation of these progenitors in adult arteries, particularly in males, may be an important mechanism contributing to the antiatherogenic effects of moderate alcohol consumption.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.14415","type":"journal-article","created":{"date-parts":[[2020,7,16]],"date-time":"2020-07-16T08:50:18Z","timestamp":1594889418000},"page":"1734-1746","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Moderate Alcohol Consumption Targets S100\u03b2<sup>+<\/sup> Vascular Stem Cells and Attenuates Injury\u2010Induced Neointimal Hyperplasia"],"prefix":"10.1111","volume":"44","author":[{"given":"Weimin","family":"Liu","sequence":"first","affiliation":[{"name":"From the Department of Surgery University of Rochester Medical Center Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzie","family":"Harman","sequence":"additional","affiliation":[{"name":"Vascular Biology and Therapeutics Laboratory School of Biotechnology Dublin City University Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana","family":"DiLuca","sequence":"additional","affiliation":[{"name":"Vascular Biology and Therapeutics Laboratory School of Biotechnology Dublin City University Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise","family":"Burtenshaw","sequence":"additional","affiliation":[{"name":"Vascular Biology and Therapeutics Laboratory School of Biotechnology 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