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Moderate alcohol consumption targets S100β+ vascular stem cells and attenuates injury-induced neointimal hyperplasia

Liu, Weimin, Harman, Suzie, Di Luca, Mariana, Burtenshaw, Denise, Corcoran, Eoin, Cahill, Paul A. orcid logoORCID: 0000-0002-5385-6502 and Redmond, Eileen M. orcid logoORCID: 0000-0001-8642-4418 (2020) Moderate alcohol consumption targets S100β+ vascular stem cells and attenuates injury-induced neointimal hyperplasia. Alcoholism: Clinical and Experimental Research, 44 (9). pp. 1734-1746. ISSN 0145-6008

Background Stem cells present in the vessel wall may be triggered in response to injurious stimuli to undergo differentiation and contribute to vascular disease development. Our aim was to determine the effect of moderate alcohol (EtOH) exposure on the expansion and differentiation of S100 calcium-binding protein B positive (S100β+) resident vascular stem cells and their contribution to pathologic vessel remodeling in a mouse model of arteriosclerosis. Methods and Results Lineage tracing analysis of S100β+ cells was performed in male and female S100β-eGFP/Cre/ERT2–dTomato transgenic mice treated daily with or without EtOH by oral gavage (peak BAC: 15 mM or 0.07%) following left common carotid artery ligation for 14 days. Carotid arteries (ligated or sham-operated) were harvested for morphological analysis and confocal assessment of fluorescent-tagged S100 β + cells in FFPE carotid cross sections. Ligation-induced carotid remodeling was more robust in males than in females. EtOH-gavaged 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 S100β+-marked cells in vessels postligation, primarily in the neointimal compartment. EtOH treatment reduced the fraction of S100β+ cells in carotid cross sections, concomitant with attenuated remodeling. In vitro, EtOH attenuated Sonic Hedgehog-stimulated myogenic differentiation (as evidenced by reduced calponin and myosin heavy chain expression) of isolated murine S100β+ vascular stem cells. Conclusions These data highlight resident vascular S100β+ 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.
Item Type:Article (Published)
Uncontrolled Keywords:Alcohol; Atherosclerosis; Cardioprotective; Gender Differences; Stem Cells; S100b.
DCU Faculties and Centres:DCU Faculties and Schools > Faculty of Science and Health > School of Biotechnology
Official URL:https://doi.org/10.1111/acer.14415
Copyright Information:© 2021 The Authors. Open Access (CC-BY 4.0)
Funders:National Institutes of Health R21AA023213 and RO1AA024082, Science Foundation Ireland grant SFI-11/PI/1128, Health Research Board of Ireland (HRB) grant HRA-POR-2015-1315, European Union’s INTERREG VA Programme, managed by the Special EU Programmes Body (SEUPB)
ID Code:27807
Deposited On:28 Sep 2022 16:07 by Thomas Murtagh . Last Modified 28 Sep 2022 16:07

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