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首页> 外文期刊>The journals of gerontology.Series A. Biological sciences and medical sciences >Mechanisms of dysfunction in senescent pulmonary endothelium.
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Mechanisms of dysfunction in senescent pulmonary endothelium.

机译:衰老的肺内皮功能障碍的机制。

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摘要

Age-dependent changes in pulmonary endothelium contribute to worsened clinical outcomes in elderly individuals. Due to altered pulmonary endothelial responses, older participants have increased vulnerability to infection-related sequelae, higher prevalence of pulmonary hypertension, mitigated DNA repair mechanisms, and attenuated parenchymal healing. Aberrant signaling in pulmonary endothelium undergird these clinical processes. In this review, we provide an overview of the work that has elucidated age-related molecular derangements in pulmonary endothelial cells. In particular, we summarize studies describing mishandling of intracellular reactive oxygen species, pathological nitric oxide signaling, and deficient recruitment of endothelial stem cell precursors. We conclude with a summary of potential future avenues of investigation. The signaling pathways associated with pulmonary endothelial senescence reviewed herein suggest a number of putative therapeutic drug targets. Further elucidation of the cellular processes associated with aging in the pulmonary endothelium may provide critical insights into the rational design of therapies that may subvert or even reverse the effects of aging on a molecular level.
机译:肺内皮的年龄依赖性变化会导致老年患者的临床结局恶化。由于肺血管内皮反应的改变,年龄较大的参与者对感染相关后遗症的脆弱性增加,肺动脉高压的患病率更高,DNA修复机制减弱,实质愈合减弱。肺内皮的异常信号传导影响了这些临床过程。在这篇综述中,我们提供了阐明肺内皮细胞中与年龄相关的分子排列紊乱的工作的概述。特别地,我们总结了描述细胞内活性氧种类处理不当,病理性一氧化氮信号传导和内皮干细胞前体募集不足的研究。最后,我们总结了未来可能的调查途径。本文综述的与肺血管内皮衰老相关的信号传导途径提示了许多推定的治疗药物靶标。进一步阐明与肺血管内皮衰老相关的细胞过程可能为合理设计疗法提供关键见解,这些疗法可能会破坏甚至逆转衰老在分子水平上的影响。

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