Alcohol Reduces Arterial Remodeling by Inhibiting Sonic Hedgehog-Stimulated Stem Cell Antigen-1 Positive Progenitor Stem Cell Expansion.
Alcohol Reduces Arterial Remodeling by Inhibiting Sonic Hedgehog-Stimulated Stem Cell Antigen-1 Positive Progenitor Stem Cell Expansion.
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DOI：
10.1111/acer.13499
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发表时间：
2017-12
期刊：
影响因子：
--
通讯作者：
Redmond EM
中科院分区：
文献类型：
--
作者：
Fitzpatrick E;Han X;Liu W;Corcoran E;Burtenshaw D;Morrow D;Helt JC;Cahill PA;Redmond EM
调节酒精对心血管影响的细胞和分子机制尚未完全了解。我们的目的是确定适度乙醇（EtOH）对Sonic Hedgehog（SHh）信号传导在病理性动脉重塑过程中调节可能的Sca 1+祖干细胞参与的影响。在用或不用"每日中度" EtOH灌胃的转基因Sca1-eGFP小鼠中进行左颈动脉的部分结扎或假手术。与结扎对照组相比，EtOH组外膜增厚减少，新生内膜形成减少。存在eGFP表达的扩增（即，Sca 1+）细胞在结扎后（14天）重塑的血管中，特别是在新生内膜中。与对照结扎血管相比，乙醇处理减少了结扎血管横截面中Sca1+细胞的数量，同时减少了重塑。此外，乙醇衰减SHh信号在损伤的颈动脉中，通过免疫组化分析的靶基因patch1（Ptch 1）和Gli2，和RT-PCR的全血管Gli2 mRNA水平。腹腔注射SHh信号抑制剂cyclopamine可降低hedgehog靶基因的表达，减少Sca 1+细胞的数量，并改善颈动脉重塑。EtOH处理纯化的Sca1+外膜祖干细胞在体外抑制SHh信号，和他们的rSHh诱导的分化为血管平滑肌细胞。EtOH在体外和在体内响应于结扎损伤的动脉重塑期间减少SHh响应性Sca 1+祖细胞肌源性分化/扩增。以这种方式调节血管Sca 1+祖细胞可能是酒精对心血管保护作用的重要新机制。
Cell and molecular mechanisms mediating the cardiovascular effects of alcohol are not fully understood. Our aim was to determine the effect of moderate Ethanol (EtOH) on Sonic Hedgehog (SHh) signaling in regulating possible Sca1+ progenitor stem cell involvement during pathologic arterial remodeling. Partial ligation or sham-operation of the left carotid artery was performed in transgenic Sca1-eGFP mice gavaged with or without ‘daily moderate’ EtOH. The EtOH group had reduced adventitial thickening and less neo-intimal formation, compared to ligated controls. There was expansion of eGFP expressing (i.e., Sca1+) cells in remodeled vessels post-ligation (14d), especially in the neo-intima. Ethanol treatment reduced the number of Sca1+ cells in ligated vessel cross-sections concomitant with diminished remodeling, compared to control ligated vessels. Moreover, EtOH attenuated SHh signaling in injured carotids as determined by immunohistochemical analysis of the target genes patched 1 (Ptch1) and Gli2, and RT-PCR of whole vessel Gli2 mRNA levels. Intraperitoneal injection of ligated Sca1 - eGFP mice with the SHh signaling inhibitor cyclopamine diminished hedgehog target gene expression, reduced the number of Sca1+ cells, and ameliorated carotid remodeling. EtOH treatment of purified Sca1+ adventitial progenitor stem cells in vitro inhibited SHh signaling, and their rSHh-induced differentiation to vascular smooth muscle cells. EtOH reduces SHh - responsive Sca1+ progenitor cell myogenic differentiation/expansion in vitro and during arterial remodeling in response to ligation injury in vivo. Regulation of vascular Sca1+ progenitor cells in this way may be an important novel mechanism contributing to alcohol's cardiovascular protective effects.
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影响因子：
8.8
作者：
Chen PY;Qin L;Barnes C;Charisse K;Yi T;Zhang X;Ali R;Medina PP;Yu J;Slack FJ;Anderson DG;Kotelianski V;Wang F;Tellides G;Simons M
通讯作者：
Simons M
影响因子：
168.9
作者：
Lozano, Rafael;Naghavi, Mohsen;Murray, Christopher J. L.
通讯作者：
Murray, Christopher J. L.
DOI：
10.1152/ajpheart.00160.2012
发表时间：
2012-12-01
影响因子：
4.8
作者：
Li, Haijie;Li, Jingjing;Zheng, Xi-Long
通讯作者：
Zheng, Xi-Long
影响因子：
2.8
作者：
Hao, Guang;Wang, Zengwu;Zhu, Manlu
通讯作者：
Zhu, Manlu
DOI：
10.1152/ajplung.00415.2002
发表时间：
2003-06-01
影响因子：
4.9
作者：
Kotton, DN;Summer, RS;Fine, A
通讯作者：
Fine, A