Nitric oxide prevents alveolar senescence and emphysema in a mouse model.

Nitric oxide prevents alveolar senescence and emphysema in a mouse model.
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一氧化氮可防止小鼠模型中的肺泡衰老和肺气肿。

DOI:
10.1371/journal.pone.0116504
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发表时间:
2015
期刊:
影响因子:
3.7
通讯作者:
Vaughan DE
Vaughan DE
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Boe AE;Eren M;Morales-Nebreda L;Murphy SB;Budinger GR;Mutlu GM;Miyata T;Vaughan DE

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Nω-nitro-L-arginine methyl ester (L-NAME) treatment induces arteriosclerosis and vascular senescence. Here, we report that the systemic inhibition of nitric oxide (NO) production by L-NAME causes pulmonary emphysema. L-NAME-treated lungs exhibited both the structural (alveolar tissue destruction) and functional (increased compliance and reduced elastance) characteristics of emphysema development. Furthermore, we found that L-NAME-induced emphysema could be attenuated through both genetic deficiency and pharmacological inhibition of plasminogen activator inhibitor-1 (PAI-1). Because PAI-1 is an important contributor to the development of senescence both in vitro and in vivo, we investigated whether L-NAME-induced senescence led to the observed emphysematous changes. We found that L-NAME treatment was associated with molecular and cellular evidence of premature senescence in mice, and that PAI-1 inhibition attenuated these increases. These findings indicate that NO serves to protect and defend lung tissue from physiological aging.
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