Blockade of EMAP II protects cardiac function after chronic myocardial infarction by inducing angiogenesis.
Blockade of EMAP II protects cardiac function after chronic myocardial infarction by inducing angiogenesis.
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DOI：
10.1016/j.yjmcc.2014.11.021
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发表时间：
2015-02
影响因子：
5
通讯作者：
Schwarz, Margaret A.
中科院分区：
文献类型：
--
作者：
Yuan, Chujun;Yan, Lin;Solanki, Pallavi;Vatner, Stephen F.;Vatner, Dorothy E.;Schwarz, Margaret A.
促进血管生成是保护慢性缺血性心脏损伤的关键治疗靶点。内皮单核细胞活化多肽II （EMAP II）蛋白是一种肿瘤来源的细胞因子，在癌症中具有抗血管生成特性，在心肌缺血后显著升高。我们研究了EMAP II的中和是否会诱导血管生成，并对慢性心肌梗死（MI）后的心肌功能和结构产生有益影响。EMAP II抗体（EMAP II AB）、载体或非特异性IgG （IgG）分别于小鼠永久性冠状动脉闭塞后30分钟、3、6和9天注射。与载体抗体或非特异性抗体相比，EMAP II AB显著（p<0.05）提高心肌梗死后存活率，减少瘢痕大小，减轻心力衰竭的发展，即EMAP II AB组左心室射血分数显著升高，纤维化减少24%，重要的是，EMAP II AB组梗死区有更多的肌细胞存活。为了支持血管生成机制，在接受EMAP II AB治疗的小鼠中，与IgG相比，毛细血管密度（193/HPF vs 172/HPF）、增殖内皮细胞数量翻倍和血管生成相关生物标志物上调。此外，EMAP II AB阻止了EMAP II蛋白对HUVECs体外试管形成的抑制作用。我们得出结论，阻断EMAP II诱导血管生成并改善慢性心肌梗死后的心功能，导致心肌纤维化和瘢痕形成减少，毛细血管密度增加，并保留梗死区域的活肌细胞。
Promoting angiogenesis is a key therapeutic target for protection from chronic ischemic cardiac injury. Endothelial-Monocyte-Activating-Polypeptide-II (EMAP II) protein, a tumor-derived cytokine having anti-angiogenic properties in cancer, is markedly elevated following myocardial ischemia. We examined whether neutralization of EMAP II induces angiogenesis and has beneficial effects on myocardial function and structure after chronic myocardial infarction (MI). EMAP II antibody (EMAP II AB), vehicle, or non-specific IgG (IgG) was injected ip at 30 min and 3, 6, and 9 days after permanent coronary artery occlusion in mice. EMAP II AB, compared with vehicle or non-specific antibody, significantly, p<0.05, improved the survival rate after MI, reduced scar size and attenuated the development of heart failure, i.e., left ventricular ejection fraction was significantly higher in EMAP II AB group, fibrosis was reduced by 24%, and importantly, more myocytes were alive in EMAP II AB group in the infarct area. In support of an angiogenic mechanism, capillary density (193/HPF vs. 172/HPF), doubling of the number of proliferating endothelial cells, and angiogenesis related biomarkers were upregulated in mice receiving EMAP II AB treatment as compared to IgG. Furthermore, EMAP II AB prevented EMAP II protein inhibition of in vitro tube formation in HUVECs. We conclude that blockade of EMAP II induces angiogenesis and improves cardiac function following chronic MI, resulting in reduced myocardial fibrosis and scar formation and increased capillary density and preserved viable myocytes in the infarct area.
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影响因子：
3.8
作者：
Berger, AC;Alexander, HR;Libutti, SK
通讯作者：
Libutti, SK
DOI：
10.1152/ajpheart.1996.270.5.h1803
发表时间：
1996-05-01
影响因子：
4.8
作者：
Li, J;Brown, LF;Simons, M
通讯作者：
Simons, M
影响因子：
64.8
作者：
Laflamme, Michael A.;Murry, Charles E.
通讯作者：
Murry, Charles E.
影响因子：
3.5
作者：
Horrigan, MCG;Malycky, JL;Nicolini, FA
通讯作者：
Nicolini, FA
影响因子：
10.8
作者：
Novoyatleva, Tatyana;Diehl, Florian;Engel, Felix B.
通讯作者：
Engel, Felix B.