风湿

端粒缩短与痛风患者相关

作者:Vazirpanah N.et al 翻译:北医三院翟佳羽 来源:中国风湿病公众论坛 日期:2017-06-19
导读

         端粒缩短与痛风患者复发次数及并发心血管疾病相关

关键字:  痛风性关节炎 

目的

        :慢性炎症与衰老相关,是心血管疾病的强有力的预测因素。在痛风中,我们假设炎症加速衰老,从而增加心血管疾病的风险。

方法:

        我们在145例荷兰痛风患者和273例健康参与者的探索队列中,通过测定端粒长度评估复制性衰老并在来自新西兰的474例痛风患者和293例健康参与者中验证我们的结果。随后,我们评估所有参与者心血管疾病对端粒长度的影响。同时,我们测定CD4+和CD8+T淋巴细胞、B淋巴细胞、单核细胞、自然杀伤细胞核浆细胞样树突状细胞的端粒长度。此外,我们评估端粒长度的潜在时间差异和端粒酶的活性。

结果

        :健康献血者外周血单个核细胞的端粒长度随时间下降,表现出正常的老化。痛风患者表现出更短的端粒(p=0.001,R2=0.01873)。事实上,痛风患者在任何年龄段端粒侵蚀的程度均高于健康对照者(p<0.0001,R2=0.02847)。有心血管疾病的痛风患者端粒最短,且端粒长度是痛风患者心血管疾病的独立危险因素(p=0.001)。端粒长度与痛风复发的次数呈负相关(p=0.005)。

结论

        :痛风患者端粒长度短于健康参与者,反映细胞衰老的增加。端粒缩短与痛风患者复发次数及并发心血管疾病相关。

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        附原文:

AIM AND BACKGROUND

        : Chronic inflammation associates with increased senescence, which is a strong predictor for cardiovascular disease. We hypothesised that inflammation accelerates senescence and thereby enhances the risk of cardiovascular disease in gout.

METHODS

        : We assessed replicative senescence by quantifying telomere length (TL) in a discovery cohort of 145 Dutch patients with gout and 273 healthy individuals and validated our results in 474 patients with gout and 293 healthy participants from New Zealand. Subsequently, we investigated the effect of cardiovascular disease on TL of all participants. Also, we measured TL of CD4+ and CD8+T lymphocytes, B lymphocytes, monocytes, natural killer cells and plasmacytoid dendritic cells. Additionally, we assessed the potential temporal difference in TL and telomerase activity.

RESULTS

        :TL in PBMCs of healthy donors decreased over time, reflecting normal ageing. Patients with gout demonstrated shorter telomeres (p=0.001, R2=0.01873). In fact, the extent of telomere erosion in patients with gout was higher at any age compared with healthy counterparts at any age (p<0.0001, R2=0.02847). Patients with gout with cardiovascular disease had the shortest telomeres and TL was an independent risk factor for cardiovascular disease in patients with gout (p=0.001). TL was inversely associated with the number of gouty flares (p=0.005).

CONCLUSION

        :Patients with gout have shorter telomeres than healthy participants, reflecting increased cellular senescence. Telomere shortening was associated with the number of flares and with cardiovascular disease in people with gout.

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