Apelin-13 infusion salvages the peri-infarct region to preserve cardiac function after severe myocardial injury.
Apelin-13 infusion salvages the peri-infarct region to preserve cardiac function after severe myocardial injury.
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DOI：
10.1016/j.ijcard.2016.07.263
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发表时间：
2016-11-01
影响因子：
3.5
通讯作者：
Yang, Phillip C.
中科院分区：
文献类型：
--
作者：
Chung, Wook-Jin;Cho, Ahryon;Byun, Kyunghee;Moon, Jeongsik;Ge, Xiaohu;Seo, Hye-Sun;Moon, Ejung;Dash, Rajesh;Yang, Phillip C.
Apelin-13（A13）调节心脏稳态。然而，急性心肌损伤（AMI）后输注A13的效果和机制尚未阐明。本研究旨在探讨A13对小鼠急性心肌梗死模型梗死周边区的修复作用及其机制。51只FVB/N小鼠（12周，30 g）进行AMI。损伤后一周，开始连续微泵输注A13（0.5 μg/g/天）和盐水，持续4周。在第1、2、3和5周进行双重对比MRI，包括延迟增强和锰增强MRI。每组中的四只小鼠在没有进一步输注的情况下被跟踪4周的延长时间段，并在第7周和第9周进行MRI扫描。A13输注显示，与生理盐水相比，从第1周至第4周LVEF保持不变（21.9 ± 3.2%至23.1 ± 1.7%* vs. 23.5 ± 1.7%至16.9 ± 2.8%，*p = 0.02），并持续至MI后9周（+1.4%* vs. − 9.4%，*p = 0.03）。从机制上讲，双对比MRI显示A13组从第1周至第4周梗死周围和瘢痕体积%显著降低（分别为15.1 - 7.4%和34.3 - 25.1%，p = 0.02）。A13组梗死周围区域5-乙炔基-2 ′-脱氧尿苷（EdU+）细胞显著增加（16.5 ± 3.1% vs. 8.1 ± 1.6%; p = 0.04），表明细胞有丝分裂活跃，证实了这一点。最后，外周血中CD 34+细胞的动员显著增强，梗死周围区域的APJ、纤维化和凋亡基因上调。A13通过挽救梗死周围区域来保护心脏性能，并可能有助于严重损伤心肌的永久恢复。
Apelin-13 (A13) regulates cardiac homeostasis. However, the effects and mechanism of A13 infusion after an acute myocardial injury (AMI) have not been elucidated. This study assesses the restorative effects and mechanism of A13 on the peri-infarct region in murine AMI model. 51 FVB/N mice (12 weeks, 30 g) underwent AMI. A week following injury, continuous micro-pump infusion of A13 (0.5 μg/g/day) and saline was initiated for 4-week duration. Dual contrast MRI was conducted on weeks 1, 2, 3, and 5, consisting of delayed-enhanced and manganese-enhanced MRI. Four mice in each group were followed for an extended period of 4 weeks without further infusion and underwent MRI scans on weeks 7 and 9. A13 infusion demonstrated preserved LVEF compared to saline from weeks 1 to 4 (21.9 ± 3.2% to 23.1 ± 1.7%* vs. 23.5 ± 1.7% to 16.9 ± 2.8%, *p = 0.02), which persisted up to 9 weeks post-MI (+1.4%* vs. −9.4%, *p = 0.03). Mechanistically, dual contrast MRI demonstrated significant decrease in the peri-infarct and scar % volume in A13 group from weeks 1 to 4 (15.1 to 7.4% and 34.3 to 25.1%, p = 0.02, respectively). This was corroborated by significant increase in 5-ethynyl-2′-deoxyuridine (EdU+) cells by A13 vs. saline groups in the peri-infarct region (16.5 ± 3.1% vs. 8.1 ± 1.6%; p = 0.04), suggesting active cell mitosis. Finally, significantly enhanced mobilization of CD34+ cells in the peripheral blood and up-regulation of APJ, fibrotic, and apoptotic genes in the peri-infarct region were found. A13 preserves cardiac performance by salvaging the peri-infarct region and may contribute to permanent restoration of the severely injured myocardium.
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影响因子：
168.9
作者：
Makkar, Raj R.;Smith, Rachel R.;Cheng, Ke;Malliaras, Konstantinos;Thomson, Louise E. J.;Berman, Daniel;Czer, Lawrence S. C.;Marban, Linda;Mendizabal, Adam;Johnston, Peter V.;Russell, Stuart D.;Schuleri, Karl H.;Lardo, Albert C.;Gerstenblith, Gary;Marban, Eduardo
通讯作者：
Marban, Eduardo
影响因子：
24
作者：
Amado, LC;Gerber, BL;Lima, JAC
通讯作者：
Lima, JAC
影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1016/s0735-1097(00)01133-5
发表时间：
2001-02-01
影响因子：
24
作者：
Brugada, J;Aguinaga, L;Sanz, G
通讯作者：
Sanz, G
影响因子：
24
作者：
Ellison, Georgina M.;Torella, Daniele;Nadal-Ginard, Bernardo
通讯作者：
Nadal-Ginard, Bernardo