Delivery of an engineered HGF fragment in an extracellular matrix-derived hydrogel prevents negative LV remodeling post-myocardial infarction.
Delivery of an engineered HGF fragment in an extracellular matrix-derived hydrogel prevents negative LV remodeling post-myocardial infarction.
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DOI：
10.1016/j.biomaterials.2014.12.021
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发表时间：
2015-03
期刊：
影响因子：
14
通讯作者：
Christman, Karen L.
中科院分区：
文献类型：
--
作者：
Sonnenberg, Sonya B.;Rane, Aboli A.;Liu, Cassie J.;Rao, Nikhil;Agmon, Gillie;Suarez, Sophia;Wang, Raymond;Munoz, Adam;Bajaj, Vaibhav;Zhang, Shirley;Braden, Rebecca;Schup-Magoffin, Pamela J.;Kwan, Oi Ling;De Maria, Anthony N.;Cochran, Jennifer R.;Christman, Karen L.
肝细胞生长因子(HGF)已被证明具有抗纤维化、促血管生成和心脏保护作用，但它高度不稳定，生产成本高，阻碍了其临床推广。最近，一种替代c-met激动剂的HGF片段(HGF-f)被设计成具有更高的稳定性和重组表达产量。在这项研究中，我们评估了HGF-f在细胞外基质(ECM)来源的水凝胶中作为心肌梗死(MI)潜在治疗药物的潜力。与未经处理的对照组相比，HGF-f保护心肌细胞免受血清饥饿，并诱导整个心肌细胞分离的纤维化标志物下调。与胶原凝胶相比，ECM水凝胶延长了HGF-f的释放，并且从ECM水凝胶体内释放HGF-f减轻了大鼠心肌梗死模型的负性重构，改善了面积变化分数(FAC)，并增加了小动脉密度。这些结果表明，HGF-f可能是使用重组HGF的一种可行的替代方法，并且ECM水凝胶可以用于增加生长因子的保留率和疗效。
Hepatocyte growth factor (HGF) has been shown to have anti-fibrotic, pro-angiogenic, and cardioprotective effects; however, it is highly unstable and expensive to manufacture, hindering its clinical translation. Recently, a HGF fragment (HGF-f), an alternative c-MET agonist, was engineered to possess increased stability and recombinant expression yields. In this study, we assessed the potential of HGF-f, delivered in an extracellular matrix (ECM)-derived hydrogel, as a potential treatment for myocardial infarction (MI). HGF-f protected cardiomyocytes from serum-starvation and induced down-regulation of fibrotic markers in whole cardiac cell isolate compared to the untreated control. The ECM hydrogel prolonged release of HGF-f compared to collagen gels, and in vivo delivery of HGF-f from ECM hydrogels mitigated negative remodeling, improved fractional area change (FAC), and increased arteriole density in rat myocardial infarction model. These results indicate that HGF-f may be a viable alternative to using recombinant HGF, and that an ECM hydrogel can be employed to increase growth factor retention and efficacy.
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影响因子：
64.8
作者：
NAKAMURA, T;NISHIZAWA, T;SHIMIZU, S
通讯作者：
SHIMIZU, S
影响因子：
37.8
作者：
Ono, M;Sawa, Y;Matsuda, H
通讯作者：
Matsuda, H
DOI：
10.1073/pnas.1102561108
发表时间：
2011-08-09
影响因子：
11.1
作者：
Jones, Douglas S., II;Tsai, Ping-Chuan;Cochran, Jennifer R.
通讯作者：
Cochran, Jennifer R.
DOI：
10.1111/j.1440-1746.2006.04586.x
发表时间：
2006-10-01
影响因子：
4.1
作者：
Han, Yuan-Ping
通讯作者：
Han, Yuan-Ping
DOI：
10.1073/pnas.0710228105
发表时间：
2008-02-12
影响因子：
11.1
作者：
Chen, Jian-Fu;Murchison, Elizabeth P.;Wang, Da-Zhi
通讯作者：
Wang, Da-Zhi