Endothelial Adenosine Monophosphate-Activated Protein Kinase-Alpha1 Deficiency Potentiates Hyperoxia-Induced Experimental Bronchopulmonary Dysplasia and Pulmonary Hypertension.
Endothelial Adenosine Monophosphate-Activated Protein Kinase-Alpha1 Deficiency Potentiates Hyperoxia-Induced Experimental Bronchopulmonary Dysplasia and Pulmonary Hypertension.
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DOI：
10.3390/antiox10121913
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发表时间：
2021-11-29
期刊：
影响因子：
--
通讯作者：
Shivanna B
中科院分区：
文献类型：
--
作者：
Elsaie A;Menon RT;Shrestha AK;Gowda SH;Varghese NP;Barrios RJ;Blanco CL;Konduri GG;Shivanna B
支气管肺发育不良和肺动脉高压，或BPD-PH，是严重的早产儿慢性肺部疾病，没有治愈性治疗。高氧是BPD-PH的一种已知致病因素，可激活新生鼠肺中的腺苷一磷酸活化蛋白激酶（AMPK）α1;然而，这种现象是否会增强或减轻肺损伤尚不清楚。因此，我们假设（1）内皮AMPKα1是保护新生小鼠免受高氧诱导的BPD-PH所必需的，（2）AMPKα1敲低降低了高氧暴露的新生人肺微血管内皮细胞（HPMEC）中的血管生成。我们在出生后第28天（P）对内皮AMPKα1充足和缺乏的小鼠进行了肺形态测量和超声心动图研究，这些小鼠从P1-P14暴露于21%O2（常氧）或70%O2（高氧）。我们还对对照或AMPKα1-siRNA转染的HPMEC进行了小管形成试验，暴露于21%O2或70%O2 48 h。在内皮AMPKα1缺陷小鼠中，高氧介导的肺泡和肺血管简化、肺血管重构和PH显著放大。AMPKα1 siRNA可抑制AMPKα1在HPMECs中的表达，并降低其在常氧和高氧条件下形成肾小管的能力。此外，AMPKα1敲低降低了高氧条件下增殖细胞核抗原的表达。我们的研究结果表明，AMPKα1需要减少新生小鼠高氧诱导的BPD-PH负荷，并促进HPMEC中的血管生成以限制肺损伤。
Bronchopulmonary dysplasia and pulmonary hypertension, or BPD-PH, are serious chronic lung disorders of prematurity, without curative therapies. Hyperoxia, a known causative factor of BPD-PH, activates adenosine monophosphate-activated protein kinase (AMPK) α1 in neonatal murine lungs; however, whether this phenomenon potentiates or mitigates lung injury is unclear. Thus, we hypothesized that (1) endothelial AMPKα1 is necessary to protect neonatal mice against hyperoxia-induced BPD-PH, and (2) AMPKα1 knockdown decreases angiogenesis in hyperoxia-exposed neonatal human pulmonary microvascular endothelial cells (HPMECs). We performed lung morphometric and echocardiographic studies on postnatal day (P) 28 on endothelial AMPKα1-sufficient and -deficient mice exposed to 21% O2 (normoxia) or 70% O2 (hyperoxia) from P1–P14. We also performed tubule formation assays on control- or AMPKα1-siRNA transfected HPMECs, exposed to 21% O2 or 70% O2 for 48 h. Hyperoxia-mediated alveolar and pulmonary vascular simplification, pulmonary vascular remodeling, and PH were significantly amplified in endothelial AMPKα1-deficient mice. AMPKα1 siRNA knocked down AMPKα1 expression in HPMECs, and decreased their ability to form tubules in normoxia and hyperoxia. Furthermore, AMPKα1 knockdown decreased proliferating cell nuclear antigen expression in hyperoxic conditions. Our results indicate that AMPKα1 is required to reduce hyperoxia-induced BPD-PH burden in neonatal mice, and promotes angiogenesis in HPMECs to limit lung injury.
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影响因子：
12.8
作者：
Kim J;Yang G;Kim Y;Kim J;Ha J
通讯作者：
Ha J
DOI：
10.1016/bs.enz.2016.03.003
发表时间：
2016
期刊：
The Enzymes
影响因子：
--
作者：
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通讯作者：
Washington MT
DOI：
10.1164/rccm.200902-0242oc
发表时间：
2009-12-01
影响因子：
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作者：
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影响因子：
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DOI：
10.1152/ajplung.00270.2010
发表时间：
2011-03-01
影响因子：
4.9
作者：
Chen, Shaoyi;Rong, Min;Wu, Shu
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