纤连蛋白对于心肌梗死后修复性心肌祖细胞反应是必不可少的。
Fibronectin is essential for reparative cardiac progenitor cell response after myocardial infarction.
机构信息
San Diego State University Integrated Regenerative Research Institute, San Diego, CA 92182, USA.
出版信息
Circ Res. 2013 Jul 5;113(2):115-25. doi: 10.1161/CIRCRESAHA.113.301152. Epub 2013 May 7.
RATIONALE
Adoptive transfer of cardiac progenitor cells (CPCs) has entered clinical application, despite limited mechanistic understanding of the endogenous response after myocardial infarction (MI). Extracellular matrix undergoes dramatic changes after MI and therefore might be linked to CPC-mediated repair.
OBJECTIVE
To demonstrate the significance of fibronectin (Fn), a component of the extracellular matrix, for induction of the endogenous CPC response to MI.
METHODS AND RESULTS
This report shows that presence of CPCs correlates with the expression of Fn during cardiac development and after MI. In vivo, genetic conditional ablation of Fn blunts CPC response measured 7 days after MI through reduced proliferation and diminished survival. Attenuated vasculogenesis and cardiogenesis during recovery were evident at the end of a 12-week follow-up period. Impaired CPC-dependent reparative remodeling ultimately leads to continuous decline of cardiac function in Fn knockout animals. In vitro, Fn protects and induces proliferation of CPCs via β₁-integrin-focal adhesion kinase-signal transducer and activator of transcription 3-Pim1 independent of Akt.
CONCLUSIONS
Fn is essential for endogenous CPC expansion and repair required for stabilization of cardiac function after MI.
背景
尽管对心肌梗死（MI）后内源性反应的机制理解有限，但过继转移心脏祖细胞（CPCs）已进入临床应用。MI 后细胞外基质发生剧烈变化，因此可能与 CPC 介导的修复有关。
目的
证明细胞外基质成分纤维连接蛋白（Fn）在诱导 MI 后内源性 CPC 反应中的重要性。
方法和结果
本报告表明，CPC 的存在与心脏发育过程中和 MI 后 Fn 的表达相关。在体内，通过减少增殖和减少存活，基因条件性敲除 Fn 会使 MI 后 7 天的 CPC 反应减弱。在 12 周的随访结束时，可见到恢复过程中血管生成和心肌生成的减弱。受损的 CPC 依赖性修复性重塑最终导致 Fn 敲除动物的心脏功能持续下降。在体外，Fn 通过β₁整联蛋白-粘着斑激酶-信号转导和转录激活因子 3-Pim1 而非 Akt 保护和诱导 CPC 增殖。
结论
Fn 对于 MI 后稳定心脏功能所需的内源性 CPC 扩增和修复是必需的。
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