Sonic hedgehog myocardial gene therapy: tissue repair through transient reconstitution of embryonic signaling
Sonic hedgehog myocardial gene therapy: tissue repair through transient reconstitution of embryonic signaling
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DOI：
10.1038/nm1313
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发表时间：
2005-11-01
期刊：
影响因子：
82.9
通讯作者：
Losordo, DW
中科院分区：
文献类型：
--
作者：
Kusano, KF;Pola, R;Losordo, DW
Sonic hedgehog（Shh）是胚胎发育过程中器官发育的重要调节因子。我们研究了是否心肌内基因转移裸DNA编码的人Shh（phShh）可以促进一个有利的影响，从急性和慢性心肌缺血在成年动物中的恢复，不仅通过促进新血管形成，但更广泛的影响，与胚胎发生中的作用，这种形态。Shh基因转移后，hedgehog通路在哺乳动物成纤维细胞和心肌细胞中上调。这导致在急性和慢性心肌缺血中通过增强新生血管形成、减少纤维化和心脏细胞凋亡来保护左心室功能。Shh基因转染还增强了骨髓来源的内皮祖细胞对心肌新生血管的贡献。这些数据表明，Shh基因治疗可能有相当大的治疗潜力，在个人与急性和慢性心肌缺血，触发多种营养因子的表达和组织修复在成人心脏。
Sonic hedgehog ( Shh) is a crucial regulator of organ development during embryogenesis. We investigated whether intramyocardial gene transfer of naked DNA encoding human Shh ( phShh) could promote a favorable effect on recovery from acute and chronic myocardial ischemia in adult animals, not only by promoting neovascularization, but by broader effects, consistent with the role of this morphogen in embryogenesis. After Shh gene transfer, the hedgehog pathway was upregulated in mammalian fibroblasts and cardiomyocytes. This resulted in preservation of left ventricular function in both acute and chronic myocardial ischemia by enhanced neovascularization, and reduced fibrosis and cardiac apoptosis. Shh gene transfer also enhanced the contribution of bone marrow-derived endothelial progenitor cells to myocardial neovascularization. These data suggest that Shh gene therapy may have considerable therapeutic potential in individuals with acute and chronic myocardial ischemia by triggering expression of multiple trophic factors and engendering tissue repair in the adult heart.