Congenital heart disease-associated pulmonary dysplasia and its underlying mechanisms.
Congenital heart disease-associated pulmonary dysplasia and its underlying mechanisms.
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先天性心脏病相关肺发育不良及其机制
DOI：
10.1152/ajplung.00195.2022
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发表时间：
2023-02-01
影响因子：
4.9
通讯作者：
Sun, Qi
中科院分区：
文献类型：
--
作者：
Li, De-Bao;Xu, Xiu-Xia;Hu, Yu-Qing;Cui, Qing;Xiao, Ying-Ying;Sun, Si -Juan;Chen, Li -Jun;Ye, Lin-Cai;Sun, Qi
临床观察表明，运动能力是先天性心脏病（CHD）患者生存的重要决定因素，在肺血流量（RPF）减少的儿童中下降最多。然而，其潜在机制仍不清楚。在这里，我们获得了法洛四联症患儿的人RPF肺样本，以及肺动脉结扎手术动物的小猪和大鼠RPF肺样本。我们观察到受损的肺泡化和血管化，肺发育不良的主要特征，在RPF婴儿，仔猪和大鼠的肺。RPF导致新生大鼠肺变小、发绀和体重减轻，并减少肺泡2型细胞的数量。RNA测序表明，RPF诱导的代谢和迁移，晚期肺泡发育的关键生物学过程的下调，和免疫反应的上调，这是通过流式细胞术和细胞因子检测证实。此外，免疫抑制剂环孢霉素A挽救了肺发育不良，并增加了Wnt信号通路的表达，这是出生后肺发育的驱动因素。我们的结论是，RPF导致肺发育不良，这可能是冠心病患者的RPF运动能力下降。其潜在机制与免疫应答激活有关，免疫抑制剂对CHD相关肺发育不良具有治疗作用。
Clinical observation indicates that exercise capacity, an important determinant of survival in patients with congenital heart disease (CHD), is most decreased in children with reduced pulmonary blood flow (RPF). However, the underlying mechanism remains unclear. Here, we obtained human RPF lung samples from children with tetralogy of Fallot as well as piglet and rat RPF lung samples from animals with pulmonary artery banding surgery. We observed impaired alveolarization and vascularization, the main characteristics of pulmonary dysplasia, in the lungs of RPF infants, piglets, and rats. RPF caused smaller lungs, cyanosis, and body weight loss in neonatal rats and reduced the number of alveolar type 2 cells. RNA-sequencing demonstrated that RPF induced the downregulation of metabolism and migration, a key biological process of late alveolar development, and the upregulation of immune response, which was confirmed by flow cytometry and cytokine detection. In addition, the immunosuppressant cyclosporine A rescued pulmonary dysplasia and increased the expression of the Wnt signaling pathway, which is the driver of postnatal lung development. We concluded that RPF results in pulmonary dysplasia, which may account for the reduced exercise capacity of CHD patients with RPF. The underlying mechanism is associated with immune response activation, and immunosuppressants have a therapeutic effect in CHD-associated pulmonary dysplasia.
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影响因子：
3.5
作者：
Abassi, Hamouda;Gavotto, Arthur;Amedro, Pascal
通讯作者：
Amedro, Pascal
影响因子：
3.1
作者：
Crowley, George;Kwon, Sophia;Nolan, Anna
通讯作者：
Nolan, Anna
DOI：
10.1165/ajrcmb.23.2.3904
发表时间：
2000-08-01
影响因子：
6.4
作者：
McGowan, S;Jackson, SK;Snyder, JM
通讯作者：
Snyder, JM
影响因子：
37.8
作者：
Diller, GP;Dimopoulos, K;Gatzoulis, MA
通讯作者：
Gatzoulis, MA
影响因子：
9.6
作者：
Gläser, S;Optiz, CF;Kleber, FX
通讯作者：
Kleber, FX