Differential expression of embryonic epicardial progenitor markers and localization of cardiac fibrosis in adult ischemic injury and hypertensive heart disease.
Differential expression of embryonic epicardial progenitor markers and localization of cardiac fibrosis in adult ischemic injury and hypertensive heart disease.
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DOI：
10.1016/j.yjmcc.2013.10.005
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发表时间：
2013-12
影响因子：
5
通讯作者：
Yutzey, Katherine E.
中科院分区：
文献类型：
--
作者：
Braitsch, Caitlin M.;Kanisicak, Onur;van Berlo, Jop H.;Molkentin, Jeffery D.;Yutzey, Katherine E.
在胚胎心脏发育过程中，转录因子Tcf21、Wt1和Tbx18调节心外膜衍生细胞（包括成纤维细胞谱系）的活化和分化。在心血管疾病小鼠模型和人类患病心脏中检测这些心外膜祖细胞因子的表达和心脏纤维化的定位。在小鼠缺血性损伤后，心外膜纤维化在表达Wt1、Tbx18和Tcf21的心外膜下细胞的增厚层中是明显的。在压力超负荷或高血压性心脏病的小鼠模型中，血管周围纤维化主要表达Tcf21，而不是Wt1或Tbx18，但在缺血性损伤后不发生。缺血性和高血压心脏的间质纤维化区域积极表达Tcf21、Wt1和Tbx18。在纤维化的所有区域中，表达心外膜祖细胞因子的细胞不同于CD45阳性免疫细胞。在人类患病心脏中，TCF 21、WT 1和TBX 18的差异表达也在心外膜、血管周围和间质纤维化中检测到，表明小鼠和人类心脏纤维化中重新激活的发育机制的保守性。总之，这些数据为不同的纤维化机制提供了证据，包括Tcf21，与Wt1和Tbx18分开，在不同的成纤维细胞群体中响应特定类型的心脏损伤。
During embryonic heart development, the transcription factors Tcf21, Wt1, and Tbx18 regulate activation and differentiation of epicardium-derived cells, including fibroblast lineages. Expression of these epicardial progenitor factors and localization of cardiac fibrosis was examined in mouse models of cardiovascular disease and in human diseased hearts. Following ischemic injury in mice, epicardial fibrosis is apparent in the thickened layer of subepicardial cells that express Wt1, Tbx18, and Tcf21. Perivascular fibrosis with predominant expression of Tcf21, but not Wt1 or Tbx18, occurs in mouse models of pressure overload or hypertensive heart disease, but not following ischemic injury. Areas of interstitial fibrosis in ischemic and hypertensive hearts actively express Tcf21, Wt1, and Tbx18. In all areas of fibrosis, cells that express epicardial progenitor factors are distinct from CD45-positive immune cells. In human diseased hearts, differential expression of TCF21, WT1, and TBX18 also is detected with epicardial, perivascular, and interstitial fibrosis, indicating conservation of reactivated developmental mechanisms in cardiac fibrosis in mice and humans. Together, these data provide evidence for distinct fibrogenic mechanisms that include Tcf21, separate from Wt1 and Tbx18, in different fibroblast populations in response to specific types of cardiac injury.
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影响因子：
3.4
作者：
Crawford, Jeffrey R.;Haudek, Sandra B.;Cieslik, Katarzyna A.;Trial, JoAnn;Entman, Mark L.
通讯作者：
Entman, Mark L.
影响因子：
20.1
作者：
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影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
Borvendég, J
影响因子：
2.5
作者：
Lincoln, J;Alfieri, CM;Yutzey, KE
通讯作者：
Yutzey, KE