Apoetm1Unc mice have impaired alveologenesis, low lung function, and rapid loss of lung function
Apoetm1Unc mice have impaired alveologenesis, low lung function, and rapid loss of lung function
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DOI：
10.1152/ajplung.00013.2008
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发表时间：
2008-05-01
影响因子：
4.9
通讯作者：
Massaro, Gloria DeCarlo
中科院分区：
文献类型：
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作者：
Massaro, Donald;Massaro, Gloria DeCarlo
吸烟者和从不吸烟者的肺功能减退，以一秒用力呼气量低(FEV1)和身材矮小为标志，预示着包括心血管在内的所有原因的早期死亡。这些关联的基础尚不清楚，也不知道在普通人群中，低FEV1与早期死亡之间是否存在肺形态成分的关系。一些载脂蛋白E基因型别也可以预测动脉粥样硬化和早期死亡率。这些考虑导致我们研究了APOE(Tm1Unc)(APOE)小鼠，在APOE小鼠中，载脂蛋白E基因被缺失，并且在早期就会患上血脂异常、动脉粥样硬化，并且比创始人野生型(Wt)品系的寿命更短。我们询问APOE小鼠是否具有形态或功能的肺表型。我们测量了肺气体交换单位(肺泡)的大小、数量和表面积以及肺的机械性能。与wt小鼠相比，apoe小鼠具有以下特点：1)发育中的肺泡形成减少，2)成年期早期呼吸道阻力增加，3)成年后期肺容量增加，动态顺应性和静态顺应性增加，4)肺反冲随年龄增加而迅速消失，5)比wt小鼠更短。在小鼠身上的这些发现表明，低FEV1与人类早期死亡的关联可能与发育和加速衰老相关的肺成分有关，并且饮食、遗传或饮食和遗传对脂肪代谢的影响可能是炎症和氧化应激的上游原因，目前被认为是COPD的主要风险因素。
Diminished lung function, indicated by a low forced expiratory volume in one second (FEV1), and short physical stature, predict early mortality from all causes, including cardiovascular, among smokers and never smokers. The basis for these associations is unclear, and, it is not known if there is a pulmonary morphological component to the relationship between low FEV1 and early death in a general population. Some apolipoprotein E genotypes also predict atherosclerosis and early mortality. These considerations led us to examine the Apoe(tm1Unc) (Apoe) mouse, in which the apolipoprotein E gene is deleted, and that develops dyslipidemia, atherosclerosis at an early age, and has a shorter life span than the founder wild-type (wt) strain. We asked if Apoe mice have a morphological or functional pulmonary phenotype. We measured the size, number, and surface area of pulmonary gas-exchange units ( alveoli) and mechanical properties of the lung. Compared with wt mice, Apoe mice had: 1) diminished developmental alveologenesis, 2) increased airway resistance in early adulthood, 3) high lung volume and high dynamic and static compliance in later adulthood, 4) more rapid loss of lung recoil with age, and 5) were less long than wt mice. These findings in mice indicate the association of a low FEV1 with early death in humans may have developmental, and accelerated ageing, related pulmonary components, and that dietary, genetic, or dietary and genetic influences, on lipid metabolism may be an upstream cause of inflammation and oxidative stress, currently considered to be major risk factors for COPD.