PlGF repairs myocardial ischemia through mechanisms of angiogenesis, cardioprotection and recruitment of myo-angiogenic competent marrow progenitors.
PlGF repairs myocardial ischemia through mechanisms of angiogenesis, cardioprotection and recruitment of myo-angiogenic competent marrow progenitors.
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DOI：
10.1371/journal.pone.0024872
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Asahara T
中科院分区：
文献类型：
--
作者：
Iwasaki H;Kawamoto A;Tjwa M;Horii M;Hayashi S;Oyamada A;Matsumoto T;Suehiro S;Carmeliet P;Asahara T
尽管使用血管生成生长因子或骨髓（BM）细胞在梗死心脏再生和血运重建方面取得了临床前成功，但最近的临床试验显示，这些疗法的益处不如预期。我们探索了胎盘生长因子（PlGF）心肌基因治疗的治疗潜力，PlGF是一种与vegf相关的血管生成生长因子，具有祖细胞动员活性。心肌PlGF基因治疗通过上调旁分泌抗凋亡因子和血管生成因子，诱导心脏修复和修复性心肌血管生成，从而改善心肌梗死后的心脏功能。此外，PlGF治疗刺激了Sca-1+/Lin - (SL) BM祖细胞的增殖，增强了它们向外周血的动员，并促进了它们向梗死周围边界的募集。此外，PlGF增强了脑梗死源性SL细胞内皮祖集落的形成，并诱导脑梗死源性SL细胞向内皮细胞、平滑肌细胞和心肌细胞谱系的表型转换。PlGF对心脏修复和再生的多效性作用为缺血性心脏病的治疗提供了新的机会。
Despite preclinical success in regenerating and revascularizing the infarcted heart using angiogenic growth factors or bone marrow (BM) cells, recent clinical trials have revealed less benefit from these therapies than expected. We explored the therapeutic potential of myocardial gene therapy of placental growth factor (PlGF), a VEGF-related angiogenic growth factor, with progenitor-mobilizing activity. Myocardial PlGF gene therapy improves cardiac performance after myocardial infarction, by inducing cardiac repair and reparative myoangiogenesis, via upregulation of paracrine anti-apoptotic and angiogenic factors. In addition, PlGF therapy stimulated Sca-1+/Lin− (SL) BM progenitor proliferation, enhanced their mobilization into peripheral blood, and promoted their recruitment into the peri-infarct borders. Moreover, PlGF enhanced endothelial progenitor colony formation of BM-derived SL cells, and induced a phenotypic switch of BM-SL cells, recruited in the infarct, to the endothelial, smooth muscle and cardiomyocyte lineage. Such pleiotropic effects of PlGF on cardiac repair and regeneration offer novel opportunities in the treatment of ischemic heart disease.