Left Ventricular Unloading After Acute Myocardial Infarction Reduces MMP/JNK Associated Apoptosis and Promotes FAK Cell-Survival Signaling
Left Ventricular Unloading After Acute Myocardial Infarction Reduces MMP/JNK Associated Apoptosis and Promotes FAK Cell-Survival Signaling
复制标题
急性心肌梗塞后左心室减负荷可减少 MMP/JNK 相关细胞凋亡并促进 FAK 细胞生存信号传导
DOI：
10.1016/j.athoracsur.2016.05.007
复制
发表时间：
2016
影响因子：
4.6
通讯作者：
Griffith Bartley P.
中科院分区：
文献类型：
--
作者：
Li Tieluo;Wei Xufeng;Evans Charles F.;Sanchez Pablo G.;Li Shuying;Wu Zhongjun J.;Griffith Bartley P.
急性心肌梗死（MI）后机械支持下左心室重构和反向重构的机制尚不清楚。我们验证了左心室辅助装置（LVAD）卸载可以减少心肌梗死后细胞凋亡信号的假设。方法采用冠状动脉结扎术建立心肌梗死模型。8名患者在心肌梗死后的前2周内卸下LVAD，并观察10周以上。取非缺血邻近区和远区心肌组织。对凋亡基质金属蛋白酶(MMPs)-2/c-Jun n末端激酶（JNK）和促存活β 1d整合素/局灶黏附激酶（FAK）通路中的蛋白进行定量。结果心肌梗死组TUNEL（末端脱氧核苷酸转移酶介导dUTP缺口末端标记）阳性细胞核增多，LVAD组TUNEL阳性细胞核增多（6.18±0.26 vs 0.82±0.18,p <0.05）。仅mi组邻区Pro-MMP-2、MMP-2、JNK和磷酸化(p)-JNK均升高，而lvad支持组邻区无升高。lvad支持组的促生存p-FAK水平高于心肌梗死组。结论心肌梗死后成年羊非缺血邻区smmp -2/JNK凋亡通路和β 1d -整合素/FAK存活通路被激活。LVAD卸载约50%心输出量2周后，部分由于其对拉伸诱导的细胞凋亡和抑制MMP-2活性的负面影响，减缓了重构。
BackgroundThe mechanism underlying left ventricular remodeling and reverse remodeling in the setting of mechanical support following acute myocardial infarction (MI) is unclear. We tested the hypothesis that left ventricular assist device (LVAD) unloading can decrease apoptotic signals after MI.MethodsAn MI model was created in 16 sheep by coronary artery ligation. Eight were unloaded with a LVAD during the first 2 weeks after MI and observed for 10 more weeks. Myocardial tissue was collected from the nonischemic adjacent zone and the remote zone. Proteins in the apoptotic matrix metalloproteinases (MMPs)-2/c-Jun N-terminal kinase (JNK) and prosurvival β1D-integrin/focal adhesion kinase (FAK) pathway were quantified.ResultsIncreased TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) positive nuclei were observed in the MI group and to a lesser extent in the LVAD group (6.18 ± 0.26 versus 0.82 ± 0.18;p <0.05). Pro-MMP-2, MMP-2, JNK, and phosphorylated (p)-JNK were all elevated in the adjacent zone of the MI-only group but not in the adjacent zone of the LVAD-supported group. There were higher levels of prosurvival p-FAK in the LVAD-supported group than in the MI group.ConclusionsMMP-2/JNK apoptotic and β1D-integrin/FAK survival pathways are activated in the nonischemic adjacent zone after MI in adult sheep. LVAD unloading of approximately 50% cardiac output for 2 weeks attenuates remodeling in part by its negative effect on stretch-induced apoptosis and inhibition of MMP-2 activity.