Long-term administration of recombinant canstatin prevents adverse cardiac remodeling after myocardial infarction
Long-term administration of recombinant canstatin prevents adverse cardiac remodeling after myocardial infarction
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DOI：
10.1038/s41598-020-69736-y
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发表时间：
2020-07-30
影响因子：
4.6
通讯作者：
Yamawaki, Hideyuki
中科院分区：
文献类型：
--
作者：
Sugiyama, Akira;Ito, Rumi;Yamawaki, Hideyuki
心肌梗死（MI）仍然是全世界死亡率的主要原因。非梗死区域的不良心脏重塑（例如肥大和纤维化）会导致失代偿性心力衰竭伴心功能障碍。我们以前证明，canstatin，一个C-末端片段的IV型胶原α 2链，对异丙肾上腺素诱导的心肌肥厚模型大鼠发挥抗重塑作用。在本研究中，我们研究了重组canstatin长期给药是否对MI模型大鼠的不良心脏重塑表现出心脏保护作用。结扎雄性Wistar大鼠的左前降支动脉，腹腔注射重组小鼠canstatin（20 μ g/kg/天）28天。长期应用canstatin可提高存活率，并显著抑制MI后左心室扩张和功能障碍。Canstatin显著抑制梗死区瘢痕变薄，显著抑制非梗死区心肌肥大、活化T细胞核因子核转位、间质纤维化和肌成纤维细胞增多。Canstatin显著抑制转化生长因子β 1诱导的大鼠心脏成纤维细胞向肌成纤维细胞的分化。本研究首次证明，长期给予重组canstatin对MI模型大鼠的不良心脏重构具有心脏保护作用。
Myocardial infarction (MI) still remains a leading cause of mortality throughout the world. An adverse cardiac remodeling, such as hypertrophy and fibrosis, in non-infarcted area leads to uncompensated heart failure with cardiac dysfunction. We previously demonstrated that canstatin, a C-terminus fragment of type IV collagen alpha 2 chain, exerted anti-remodeling effect against isoproterenol-induced cardiac hypertrophy model rats. In the present study, we examined whether a long-term administration of recombinant canstatin exhibits a cardioprotective effect against the adverse cardiac remodeling in MI model rats. Left anterior descending artery of male Wistar rats was ligated and recombinant mouse canstatin (20 mu g/kg/day) was intraperitoneally injected for 28 days. Long-term administration of canstatin improved survival rate and significantly inhibited left ventricular dilatation and dysfunction after MI. Canstatin significantly inhibited scar thinning in the infarcted area and significantly suppressed cardiac hypertrophy, nuclear translocation of nuclear factor of activated T-cells, interstitial fibrosis and increase of myofibroblasts in the non-infarcted area. Canstatin significantly inhibited transforming growth factor-beta 1-induced differentiation of rat cardiac fibroblasts into myofibroblasts. The present study for the first time demonstrated that long-term administration of recombinant canstatin exerts cardioprotective effects against adverse cardiac remodeling in MI model rats.