Dynamics of angiogenesis in ischemic areas of the infarcted heart.
Dynamics of angiogenesis in ischemic areas of the infarcted heart.
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DOI：
10.1038/s41598-017-07524-x
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发表时间：
2017-08-02
影响因子：
4.6
通讯作者：
Murohara T
中科院分区：
文献类型：
--
作者：
Kobayashi K;Maeda K;Takefuji M;Kikuchi R;Morishita Y;Hirashima M;Murohara T
心肌梗死(MI)急性期和亚急性期心肌细胞易受缺氧引起的细胞凋亡的影响。血管生成可通过减轻缺氧减轻心肌梗死所致的损伤。据推测，缺血边缘带是血管生成治疗所挽救的独特区域。然而，哺乳动物心脏在缺氧后形成新血管的机制和时间尚不清楚。确定受益于血管生成治疗的靶点对于革命性治疗的发展是不可或缺的。在这里，我们描述了一个新的循环系统，在这个系统中，新的血管从左心室内膜长出，向缺氧区灌流，并通过激活血管内皮生长因子信号在心肌梗死后3-14天挽救受损的心肌细胞。此外，增强的血管生成增加了缺血区沿心内膜的心肌细胞存活率，并抑制了梗死心脏的心室重构。相反，心肌梗死后12 h内缺氧区边缘区心肌细胞发生凋亡，可供治疗的边缘区消失。这些数据表明，沿着心内膜的非灌注区是血管生成活跃的部位，也是心肌梗死治疗的一个有前景的靶点。
Cardiomyocytes are susceptible to apoptosis caused by hypoxia during the acute and subacute phases of myocardial infarction (MI). Angiogenesis can reduce MI-induced damage by mitigating hypoxia. It has been speculated that the ischemic border zone is a unique area rescued by angiogenic therapy. However, the mechanism and timing for new vessel formation in the mammalian heart following hypoxia are unclear. Identifying targets that benefit from angiogenesis treatment is indispensable for the development of revolutionary therapies. Here, we describe a novel circulatory system wherein new vessels develop from the endocardium of the left ventricle to perfuse the hypoxic area and salvage damaged cardiomyocytes at 3–14 days after MI by activating vascular endothelial growth factor signaling. Moreover, enhanced angiogenesis increased cardiomyocyte survival along the endocardium in the ischemic zone and suppressed ventricular remodeling in infarcted hearts. In contrast, cardiomyocytes in the border zone’s hypoxic area underwent apoptosis within 12 h of MI, and the border area that was amenable to treatment disappeared. These data indicate that the non-perfused area along the endocardium is a site of active angiogenesis and a promising target for MI treatment.
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影响因子：
15.9
作者：
Ozawa, CR;Banfi, A;Blau, HM
通讯作者：
Blau, HM
DOI：
10.1083/jcb.129.4.895
发表时间：
1995-05
期刊：
The Journal of cell biology
影响因子：
--
作者：
Mustonen T;Alitalo K
通讯作者：
Alitalo K
影响因子：
15.9
作者：
Song, YH;Li, YX;Delafontaine, P
通讯作者：
Delafontaine, P
影响因子：
37.8
作者：
Henry, TD;Annex, BH;McCluskey, ER
通讯作者：
McCluskey, ER
影响因子：
64.8
作者：
SATO, TN;TOZAWA, Y;QIN, Y
通讯作者：
QIN, Y