Sex differences in endothelial cell function: an evolving explanation of sex differences in preterm infant pulmonary outcomes.
Sex differences in endothelial cell function: an evolving explanation of sex differences in preterm infant pulmonary outcomes.
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内皮细胞功能的性别差异：早产儿肺部结局性别差异的不断发展的解释。
DOI：
10.1152/ajpheart.00718.2022
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Sherlock,LauraG
中科院分区：
文献类型：
--
作者：
Cookson,MichaelW;Sherlock,LauraG
在过去的30年里，早产儿护理方面的进展继续取得进展，但随着妊娠不足26周的婴儿积极复苏的比例增加，早产儿慢性肺部疾病--支气管肺发育不良(BPD)的发病率继续上升。在肺发育的脆弱管状阶段早产，反复和长时间暴露于许多挽救生命的出生后干预措施，如机械通风和氧疗，扰乱了肺泡生长所需的正常细胞信号，并使这些婴儿面临肺部发育异常和晚期呼吸道疾病的高风险(1)。尽管许多孕前、产前和出生后的因素调节了个体新生儿患BPD的风险，但男性是BPD发展更严重的一个公认的风险因素。男婴的易感性增加被推测是由于性激素暴露的差异或与Y或X染色体上基因的差异表达。进一步了解男性处于不利地位的原因对于提供有针对性的治疗方法至关重要。与人类观察一致的是，使用出生后高氧诱导肺损伤的小鼠模型进行的关键临床前研究显示，与雌性小鼠相比，新生雄性小鼠的肺泡化和血管生成减少，肺炎性细胞流入增加，总体死亡率增加。用新生小鼠进行的优雅研究表明，与性腺相反，性染色体的存在对肺泡生长和血管生成的停滞影响更大。然而，性别对肺发育的细胞特异性影响的研究还不完全。内皮细胞(EC)功能障碍导致肺泡发育中断，最近使用高氧诱导的BPD模型的研究表明，内皮细胞损伤先于受损的肺泡化[5]。先前的人脐静脉内皮细胞(HUVECs)体外实验表明，在EC功能和细胞信号转导方面存在性别差异。高氧暴露后，通过测量输卵管长度，雄性人脐静脉内皮细胞显示细胞活力下降，氧化应激增加，血管生成减少。
Advances in the care of preterm neonates have continued to progress over the last 30 years, but the incidence of bronchopulmonary dysplasia (BPD), the chronic lung disease of prematurity, continues to rise as the percentage of babies being actively resuscitated at less than 26 wk gestation increases (1). Preterm birth during the fragile canalicular stage of lung development with repeated and prolonged exposures to many lifesaving postnatal interventions, such as mechanical ventilation and oxygen therapy, disrupts normal cellular signaling required for alveolar growth and places these infants at high risk for aberrant lung development and late respiratory morbidity (1). Although many preconceptual, antenatal, and postnatal factors modulate an individual neonate’s risk for BPD, male sex is a well-established risk factor for more severe BPD development (2). The increased vulnerability of male infants is speculated to be due to differences in sex hormone exposure or differential expression from genes on the Y or X chromosome. A further understanding of why males are disadvantaged is essential to inform targeted therapeutics. Consistent with human observations, key preclinical studies using a mouse model of postnatal hyperoxia-induced lung injury demonstrated decreased alveolarization and angiogenesis, increased pulmonary inflammatory cell influx, and increased overall mortality in neonatal male mice as compared with females (3). Elegant studies using neonatal mice have clarified that the arrest in alveolar growth and angiogenesis is more significantly impacted by the presence of the sex chromosome, as opposed to the gonads (4). However, the cellspecific impact of sex on lung development is incompletely studied.Endothelial cell (EC) dysfunction drives the abruption in alveolar development, with recent work using a hyperoxia-induced model of BPD demonstrating that endothelial injury precedes impaired alveolarization (5). Prior in vitro work with human umbilical vein ECs (HUVECs) implicates sex differences exist in EC function and cell signaling. After hyperoxia exposure, male HUVECs demonstrate decreased cell viability, increased oxidative stress, and decreased angiogenesis by measuring tubal length