Myocardial fibrosis reversion via rhACE2-electrospun fibrous patch for ventricular remodeling prevention.

Myocardial fibrosis reversion via rhACE2-electrospun fibrous patch for ventricular remodeling prevention.
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通过rhace2 -电纺丝纤维贴片预防心室重构逆转心肌纤维化。

DOI:
10.1038/s41536-021-00154-y
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发表时间:
2021-08-10
影响因子:
7.2
通讯作者:
Jin W
Jin W
中科院分区:
医学1区
文献类型:
--
作者:
Qiu Z;Zhao J;Huang F;Bao L;Chen Y;Yang K;Cui W;Jin W

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心肌纤维化和心室重构是导致心肌梗死后不良后果的关键病理因素。然而,一种有效的治疗方法仍不清楚,部分原因是难以持续预防神经激素过度激活,以及细胞疗法在临床实践中的潜在缺点。本研究通过微溶胶电纺技术制备了一种可持续释放重组人ACE2的电纺纤维贴片,可在原位形成诱导转化位。在透明质酸(HA)-聚L-乳酸(PLLA)核壳结构中观察到重组人血管紧张素转换酶2的持久释放模式。多项体外研究表明,rhACE2贴剂具有减少缺氧应激下心肌细胞凋亡和抑制心肌成纤维细胞增殖的作用,为其体内作用提供了证据。对于急性心肌梗死小鼠的实验,已证明成功地预防了不利的心室重构,反映在射血分数的改善、正常的心室结构和较少的纤维化。与心肌内注射相比,rhACE2贴片壁龛在缺血后的长期功能和结构保存方面显示出明显的优势。因此,微溶胶电纺重组人血管紧张素转换酶2纤维贴片壁龛被证明是有效的,成本效益高,易于使用,以防止心脏的不良重构。
Myocardial fibrosis and ventricular remodeling were the key pathology factors causing undesirable consequence after myocardial infarction. However, an efficient therapeutic method remains unclear, partly due to difficulty in continuously preventing neurohormonal overactivation and potential disadvantages of cell therapy for clinical practice. In this study, a rhACE2-electrospun fibrous patch with sustained releasing of rhACE2 to shape an induction transformation niche in situ was introduced, through micro-sol electrospinning technologies. A durable releasing pattern of rhACE2 encapsulated in hyaluronic acid (HA)—poly(L-lactic acid) (PLLA) core-shell structure was observed. By multiple in vitro studies, the rhACE2 patch demonstrated effectiveness in reducing cardiomyocytes apoptosis under hypoxia stress and inhibiting cardiac fibroblasts proliferation, which gave evidence for its in vivo efficacy. For striking mice myocardial infarction experiments, a successful prevention of adverse ventricular remodeling has been demonstrated, reflecting by improved ejection fraction, normal ventricle structure and less fibrosis. The rhACE2 patch niche showed clear superiority in long term function and structure preservation after ischemia compared with intramyocardial injection. Thus, the micro-sol electrospun rhACE2 fibrous patch niche was proved to be efficient, cost-effective and easy-to-use in preventing ventricular adverse remodeling.
肾素-血管紧张素系统的 ACE2/血管紧张素 1-7 轴在心力衰竭中的作用。
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