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吸烟、miR-27b下调与外周动脉疾病:对吸烟毒性机制的见解

Cigarette Smoking, miR-27b Downregulation, and Peripheral Artery Disease: Insights into the Mechanisms of Smoking Toxicity.

作者信息

Pereira-da-Silva Tiago, Napoleão Patrícia, Costa Marina C, Gabriel André F, Selas Mafalda, Silva Filipa, Enguita Francisco J, Ferreira Rui Cruz, Carmo Miguel Mota

机构信息

Department of Cardiology, Hospital de Santa Marta, Centro Hospitalar Universitário de Lisboa Central, 1169-024 Lisbon, Portugal.

NOVA Doctoral School, NOVA Medical School|Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, 1169-056 Lisbon, Portugal.

出版信息

J Clin Med. 2021 Feb 22;10(4):890. doi: 10.3390/jcm10040890.

DOI:10.3390/jcm10040890
PMID:33671744
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7926909/
Abstract

Cigarette smoking is a risk factor for the development of peripheral artery disease (PAD), although the proatherosclerotic mediators of cigarette smoking are not entirely known. We explored whether circulating microRNAs (miRNAs) are dysregulated in cigarette smokers and associated with the presence of PAD. Ninety-four participants were recruited, including 58 individuals without and 36 with PAD, 51 never smokers, 28 prior smokers, and 15 active smokers. The relative expression of six circulating miRNAs with distinct biological roles (miR-21, miR-27b, miR-29a, miR-126, miR-146, and miR-218) was assessed. Cigarette smoking was associated with the presence of PAD in multivariate analysis. Active smokers, but not prior smokers, presented miR-27b downregulation and higher leukocyte, neutrophil, and lymphocyte counts; miR-27b expression levels were independently associated with active smoking. Considering the metabolic and/or inflammatory abnormalities induced by cigarette smoking, miR-27b was independently associated with the presence of PAD and downregulated in patients with more extensive PAD. In conclusion, the atheroprotective miR-27b was downregulated in active smokers, but not in prior smokers, and miR-27b expression was independently associated with the presence of PAD. These unreported data suggest that the proatherogenic properties of cigarette smoking are mediated by a downregulation of miR-27b, which may be attenuated by smoking cessation.

摘要

吸烟是外周动脉疾病(PAD)发生的一个风险因素,尽管吸烟促动脉粥样硬化的介质尚不完全清楚。我们探讨了吸烟者循环中的微小RNA(miRNA)是否失调以及是否与PAD的存在相关。招募了94名参与者,包括58名无PAD者和36名有PAD者,51名从不吸烟者,28名既往吸烟者和15名当前吸烟者。评估了具有不同生物学作用的六种循环miRNA(miR-21、miR-27b、miR-29a、miR-126、miR-146和miR-218)的相对表达。多因素分析显示吸烟与PAD的存在相关。当前吸烟者而非既往吸烟者出现miR-27b下调以及白细胞、中性粒细胞和淋巴细胞计数升高;miR-27b表达水平与当前吸烟独立相关。考虑到吸烟引起的代谢和/或炎症异常,miR-27b与PAD的存在独立相关,且在PAD更广泛的患者中下调。总之,具有抗动脉粥样硬化作用的miR-27b在当前吸烟者中下调,但在既往吸烟者中未下调,且miR-27b表达与PAD的存在独立相关。这些未报道的数据表明,吸烟的促动脉粥样硬化特性是由miR-27b下调介导的,戒烟可能会减弱这种作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19f3/7926909/7fc8226fe992/jcm-10-00890-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19f3/7926909/fc6fc021b921/jcm-10-00890-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19f3/7926909/7fc8226fe992/jcm-10-00890-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19f3/7926909/fc6fc021b921/jcm-10-00890-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19f3/7926909/7fc8226fe992/jcm-10-00890-g002.jpg

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