Upregulating carnitine palmitoyltransferase 1 attenuates hyperoxia-induced endothelial cell dysfunction and persistent lung injury.
Upregulating carnitine palmitoyltransferase 1 attenuates hyperoxia-induced endothelial cell dysfunction and persistent lung injury.
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DOI：
10.1186/s12931-022-02135-1
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发表时间：
2022-08-13
影响因子：
5.8
通讯作者：
中科院分区：
文献类型：
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支气管肺发育不良（BPD）是早产儿的一种慢性肺部疾病，可能导致长期肺功能障碍。越来越多的证据支持BPD的血管假说，即肺内皮细胞功能障碍驱动这种疾病。我们最近报道，内皮肉毒碱棕榈酰转移酶1a（Cpt 1a）减少高氧，内皮细胞特异性Cpt 1a基因敲除小鼠比野生型小鼠更容易发展高氧诱导的损伤。Cpt 1a上调是否能减轻高氧诱导的内皮细胞功能障碍和肺损伤仍不清楚。我们假设黄芩苷或左旋卡尼汀上调Cpt 1a可改善高氧诱导的内皮细胞功能障碍和持续性肺损伤。肺内皮细胞或新生小鼠（< 12 h龄）在高氧（50%和95% O2）后用黄芩苷或左旋卡尼汀处理，随后空气恢复。我们发现，与L-肉毒碱（40和80 mg/L）和黄芩苷（22.5和45 mg/L）孵育减少高氧诱导的细胞凋亡，受损的细胞迁移和血管生成在培养的肺内皮细胞。这与Cpt 1a基因表达增加有关。在小鼠中，新生儿高氧以浓度依赖性方式引起持续性肺泡和血管简化。治疗左旋卡尼汀（150和300毫克/公斤）和黄芩苷（50和100毫克/公斤）衰减新生儿高氧诱导的肺泡和血管简化成年小鼠。这些作用在内皮细胞特异性Cpt 1a敲除小鼠中减弱。黄芩苷或左旋卡尼汀上调Cpt 1a可改善高氧诱导的肺内皮细胞功能障碍，以及持续的肺泡和血管简化。这些发现为使用左旋卡尼汀和黄芩苷作为Cpt 1a上调剂预防BPD早产儿持续性肺损伤提供了潜在的治疗途径。
Bronchopulmonary dysplasia (BPD) is a chronic lung disease in premature infants that may cause long-term lung dysfunction. Accumulating evidence supports the vascular hypothesis of BPD, in which lung endothelial cell dysfunction drives this disease. We recently reported that endothelial carnitine palmitoyltransferase 1a (Cpt1a) is reduced by hyperoxia, and that endothelial cell-specific Cpt1a knockout mice are more susceptible to developing hyperoxia-induced injury than wild type mice. Whether Cpt1a upregulation attenuates hyperoxia-induced endothelial cell dysfunction and lung injury remains unknown. We hypothesized that upregulation of Cpt1a by baicalin or l-carnitine ameliorates hyperoxia-induced endothelial cell dysfunction and persistent lung injury. Lung endothelial cells or newborn mice (< 12 h old) were treated with baicalin or l-carnitine after hyperoxia (50% and 95% O2) followed by air recovery. We found that incubation with l-carnitine (40 and 80 mg/L) and baicalin (22.5 and 45 mg/L) reduced hyperoxia-induced apoptosis, impaired cell migration and angiogenesis in cultured lung endothelial cells. This was associated with increased Cpt1a gene expression. In mice, neonatal hyperoxia caused persistent alveolar and vascular simplification in a concentration-dependent manner. Treatment with l-carnitine (150 and 300 mg/kg) and baicalin (50 and 100 mg/kg) attenuated neonatal hyperoxia-induced alveolar and vascular simplification in adult mice. These effects were diminished in endothelial cell-specific Cpt1a knockout mice. Upregulating Cpt1a by baicalin or l-carnitine ameliorates hyperoxia-induced lung endothelial cell dysfunction, and persistent alveolar and vascular simplification. These findings provide potential therapeutic avenues for using l-carnitine and baicalin as Cpt1a upregulators to prevent persistent lung injury in premature infants with BPD.
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DOI：
10.1002/path.5534
发表时间：
2020-12
期刊：
The Journal of pathology
影响因子：
--
作者：
Gong J;Feng Z;Peterson AL;Carr JF;Vang A;Braza J;Choudhary G;Dennery PA;Yao H
通讯作者：
Yao H
DOI：
10.1292/jvms.13-0202
发表时间：
2014-01
期刊：
The Journal of veterinary medical science
影响因子：
--
作者：
Boyacioglu M;Turgut H;Akgullu C;Eryilmaz U;Kum C;Onbasili OA
通讯作者：
Onbasili OA
影响因子：
2.5
作者：
Bancalari, Eduardo;Jain, Deepak
通讯作者：
Jain, Deepak
DOI：
10.1186/s10020-021-00309-z
发表时间：
2021-05-30
期刊：
Molecular medicine (Cambridge, Mass.)
影响因子：
--
作者：
Hao D;Li Y;Shi J;Jiang J
通讯作者：
Jiang J
影响因子：
64.5
作者：
De Bock, Katrien;Georgiadou, Maria;Carmeliet, Peter
通讯作者：
Carmeliet, Peter