Combined therapy with shock wave and autologous bone marrow-derived mesenchymal stem cells alleviates left ventricular dysfunction and remodeling through inhibiting inflammatory stimuli, oxidative stress & enhancing angiogenesis in a swine myocardial infarction model
Combined therapy with shock wave and autologous bone marrow-derived mesenchymal stem cells alleviates left ventricular dysfunction and remodeling through inhibiting inflammatory stimuli, oxidative stress & enhancing angiogenesis in a swine myocardial infarction model
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DOI：
10.1016/j.ijcard.2015.03.044
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发表时间：
2015-08-15
影响因子：
3.5
通讯作者：
Yip, Hon-Kan
中科院分区：
文献类型：
--
作者：
Sheu, Jiunn-Jye;Lee, Fan-Yen;Yip, Hon-Kan
背景：我们假设冲击波 (SW) 和自体骨髓间充质干细胞 (BMDMSC) 联合治疗在缓解左心室 (LV) 功能障碍方面优于单独治疗。 方法和结果：雄性小型猪 (n = 30) 均分为第 1 组（假手术对照）、第 2 组[左冠状动脉结扎引起的急性心肌梗死 (AMI)]、第 3 组 (AMI-SW)、第 4 组(AMI-BMDMSC) 和第 5 组 (AMI-SW-BMDMSC) 在第 60 天时处死并收集心脏用于研究。基线 LV 注射分数 [LVEF (%)] 和 LV 室大小在五组之间没有差异 (p > 0.5)。到第 60 天，第 1 组的 LVEF 最高，第 2 组最低，第 5 组显着高于第 3 组和第 4 组，第 4 组显着高于第 3 组 (p < 0.001)。 VEGF、CXCR4 和 SDF-1 α 的细胞和蛋白质水平从第 1 组到第 5 组逐渐显着增加（所有 p < 0.05）。 CD31 和 eNOS 的小血管数量和蛋白表达在第 1 组和第 5 组中最高，第 2 组最低，第 4 组显着高于第 3 组 (p < 0.001)。炎症生物标志物的蛋白质（MMP-9、TNF-1α和NF-κB）和细胞（CD14（+）、CD40（+））水平、氧化应激（氧化蛋白、NOX-1、NOX-2）、细胞凋亡（Bax、caspase-3、PARP）的蛋白质表达、梗死面积和LV尺寸在所有组中显示出与LVEF相反的模式（所有p < 0.001).结论：SW-BMDMSC 联合治疗在改善 LVEF、减少梗死面积和抑制 LV 重塑方面优于单独的任一治疗。 (C) 2015 Elsevier Ireland Ltd. 保留所有权利。
Background: We hypothesized that combined therapy with shock wave (SW) and autologous bone marrow-derived mesenchymal stem cells (BMDMSCs) is superior to either therapy alone for alleviating left ventricular (LV) dysfunction.Methods and results: Male mini-pigs (n = 30) equally divided into group 1 (sham control), group 2 [acute myocardial infarction (AMI) by left coronary artery ligation], group 3 (AMI-SW), group 4 (AMI-BMDMSC), and group 5 (AMI-SW-BMDMSC) were sacrificed by day 60 and the hearts were collected for studies. Baseline LV injection fraction [LVEF (%)] and LV chamber size did not differ among the five groups (p > 0.5). By day 60, LVEF was highest in group 1 and lowest in group 2, significantly higher in group 5 than that in groups 3 and 4, and significantly higher in group 4 than that in group 3 (p < 0.001). Cellular and protein levels of VEGF, CXCR4, and SDF-1 alpha were significantly increased progressively from groups 1 to 5 (all p < 0.05). Small vessel number and protein expressions of CD31 and eNOS were highest in groups 1 and 5, lowest in group 2, and significantly higher in group 4 than those in group 3 (p < 0.001). Protein (MMP-9, TNF-1 alpha and NF-kappa B) and cellular (CD14(+), CD40(+)) levels of inflammatory biomarkers, protein expressions of oxidative stress (oxidized protein, NOX-1, NOX-2), apoptosis (Bax, caspase-3, PARP), infarct size, and LV dimensions showed a pattern opposite to that of LVEF among all groups (all p < 0.001).Conclusions: Combined SW-BMDMSC therapy is superior to either therapy alone for improving LVEF, reducing infarct size, and inhibiting LV remodeling. (C) 2015 Elsevier Ireland Ltd. All rights reserved.