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首页> 外文期刊>Drug Target Insights >Impact of Hepatocyte Growth Factor on Skeletal Myoblast Transplantation Late After Myocardial Infarction
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Impact of Hepatocyte Growth Factor on Skeletal Myoblast Transplantation Late After Myocardial Infarction

机译：肝细胞生长因子对心肌梗死后骨骼成肌细胞移植的影响

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In clinical studies, skeletal myoblast (SKMB) transplantation late after myocardial infarction (MI) has minimal impact on left ventricular (LV) function. This may be related to our previous observation that the extent of SKMB engraftment is minimal in chronic MI when compared to acute MI, which correlates with decreased hepatocyte growth factor (HGF) expression, an important regulator of SKMB function. Here, we investigated delivery of exogenous HGF as a strategy for augmenting SKMB engraftment late after MI. Rats underwent SKMB transplantation 4 weeks after coronary ligation. HGF or vehicle control was delivered intravenously during the subsequent 2 weeks. LV function was assessed by MRI before and 2 weeks after SKMB transplantation. We evaluated HGF delivery, SKMB engraftment, and expression of genes associated with post-MI remodeling. Serum HGF was 6.2 ± 2.4 ng/mL after 2 weeks of HGF infusion (n = 7), but undetectable in controls (n = 7). LV end-diastolic volume and ejection fraction did not improve with HGF treatment (321 ± 27 mm3, 42% ± 2% vs. 285 ± 33 mm3, 43% ± 2%, HGF vs. control). MIs were larger in HGF-treated animals (50 ± 7 vs. 30 ± 6 mm3, P = 0.046), but the volume of engrafted SKMBs or percentage of MIs occupied by SKMBs did not increase with HGF (1.7 ± 0.3 mm3, 4.7% ± 1.9% vs. 1.4 ± 0.4 mm3, 5.3% ± 1.6%, HGF vs. control). Expression of genes associated with post-infarction remodeling was not altered by HGF. Delivery of exogenous HGF failed to augment SKMB engraftment and functional recovery in chronic MI. Expression of genes associated with LV remodeling was not altered by HGF. Alternative strategies to enhance engraftment of SKMB must be explored to optimize the clinical efficacy of SKMB transplantation.
机译：在临床研究中，心肌梗死（MI）后晚期骨骼肌成肌细胞（SKMB）移植对左心室（LV）功能的影响极小。这可能与我们先前的观察结果有关，即与急性心肌梗死相比，慢性心肌梗死中SKMB的植入程度很小，这与肝细胞生长因子（HGF）表达的下降有关，肝生长因子是SKMB功能的重要调节剂。在这里，我们调查了外源性HGF的传递，作为增加MI后晚期SKMB植入的策略。大鼠在冠状动脉结扎后4周进行SKMB移植。在随后的2周内静脉内注射HGF或媒介物对照。在SKMB移植之前和之后2周，​​通过MRI评估LV功能。我们评估了HGF的传递，SKMB的植入以及MI后重塑相关基因的表达。输注HGF 2周后，血清HGF为6.2±2.4 ng / mL（n = 7），但在对照中未检测到（n = 7）。 HGF治疗后左室舒张末期容积和射血分数没有改善（321±27 mm3，42％±2％vs. 285±33 mm3，43％±2％，HGF vs.对照）。在接受HGF的动物中，MI较大（50±7 vs. 30±6 mm3，P = 0.046），但是随着HGF的植入，SKMB的体积或SKMB所占MI的百分比并未增加（1.7±0.3 mm3，4.7％）。 ±1.9％与1.4±0.4 mm3、5.3％±1.6％，HGF与对照的对比）。 HGF不会改变与梗死后重塑相关的基因的表达。在慢性心肌梗死中，外源HGF的递送未能增加SKMB的植入和功能恢复。 HGF不会改变与LV重塑相关的基因的表达。必须探索增强SKMB植入的替代策略，以优化SKMB移植的临床疗效。

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