FN3K expression in COPD: a potential comorbidity factor for cardiovascular disease.
FN3K expression in COPD: a potential comorbidity factor for cardiovascular disease.
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DOI：
10.1136/bmjresp-2020-000714
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发表时间：
2020-11
影响因子：
4.1
通讯作者：
Kirkham P
中科院分区：
文献类型：
--
作者：
Alderawi A;Caramori G;Baker EH;Hitchings AW;Rahman I;Rossios C;Adcock I;Cassolari P;Papi A;Ortega VE;Curtis JL;Dunmore S;Kirkham P
吸烟和氧化应激是慢性阻塞性肺疾病（COPD）多发病的常见危险因素。晚期糖基化终产物（AGE）水平升高可增加心血管疾病（CVD）合并症和死亡率的风险。果糖胺-3-激酶（FN 3 K）通过降低AGE水平来降低这种风险。采用免疫组织化学方法检测稳定期COPD患者、对照组及COPD动物模型肺组织中FN 3 K蛋白的分布和表达。采用ELISA法评估接受二甲双胍治疗的COPD急性加重患者的血清FN 3 K蛋白和AGE水平。在COPD研究队列的亚群和中间结果指标中，评价了FN 3 K和FN 3 K-RP基因内的遗传变异与心肺功能的相关性。这项初步研究表明，FN 3 K在血液和人肺上皮细胞中的表达以高或低水平分布，与疾病状态无关。在肺功能正常的对照吸烟者中，表达FN 3 K的肺上皮细胞的百分比较高，但在COPD患者和COPD吸烟模型中均未观察到这种诱导。可能与心肺功能降低相关的前五个标称FN 3 K多态性（p<0.008-0.02）在多重比较分析后均未达到被认为高度显著的阈值（p<0.0028）。Metastasis增强COPD受试者的FN 3 K全身水平，与其高表达或低表达状态无关。这些数据强调了在我们的研究队列中存在低和高FN 3 K表达者，二甲双胍诱导FN 3 K水平，突出了降低CVD合并症和死亡率风险的潜在机制。
Cigarette smoking and oxidative stress are common risk factors for the multi-morbidities associated with chronic obstructive pulmonary disease (COPD). Elevated levels of advanced glycation endproducts (AGE) increase the risk of cardiovascular disease (CVD) comorbidity and mortality. The enzyme fructosamine-3-kinase (FN3K) reduces this risk by lowering AGE levels. The distribution and expression of FN3K protein in lung tissues from stable COPD and control subjects, as well as an animal model of COPD, was assessed by immunohistochemistry. Serum FN3K protein and AGE levels were assessed by ELISA in patients with COPD exacerbations receiving metformin. Genetic variants within the FN3K and FN3K-RP genes were evaluated for associations with cardiorespiratory function in the Subpopulations and Intermediate Outcome Measures in COPD Study cohort. This pilot study demonstrates that FN3K expression in the blood and human lung epithelium is distributed at either high or low levels irrespective of disease status. The percentage of lung epithelial cells expressing FN3K was higher in control smokers with normal lung function, but this induction was not observed in COPD patients nor in a smoking model of COPD. The top five nominal FN3K polymorphisms with possible association to decreased cardiorespiratory function (p<0.008–0.02), all failed to reach the threshold (p<0.0028) to be considered highly significant following multi-comparison analysis. Metformin enhanced systemic levels of FN3K in COPD subjects independent of their high-expression or low-expression status. The data highlight that low and high FN3K expressors exist within our study cohort and metformin induces FN3K levels, highlighting a potential mechanism to reduce the risk of CVD comorbidity and mortality.
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DOI：
10.1183/13993003.00202-2017
发表时间：
2017-11
期刊：
The European respiratory journal
影响因子：
--
作者：
Michaeloudes C;Kuo CH;Haji G;Finch DK;Halayko AJ;Kirkham P;Chung KF;Adcock IM;COPDMAP
通讯作者：
COPDMAP
影响因子：
4.3
作者：
Allaman I;Bélanger M;Magistretti PJ
通讯作者：
Magistretti PJ
影响因子：
--
作者：
Ghanbari, Mohsen;Franco, Oscar H.;Dehghan, Abbas
通讯作者：
Dehghan, Abbas
影响因子：
3.1
作者：
Fukami, Kei;Yamagishi, Sho-ichi;Okuda, Seiya
通讯作者：
Okuda, Seiya
影响因子：
9.8
作者：
Benton, Miles C.;Lea, Rod A.;Griffiths, Lyn R.
通讯作者：
Griffiths, Lyn R.