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不稳定冠状动脉斑块中中性粒细胞的端粒酶活性高。

High telomerase activity in neutrophils from unstable coronary plaques.

作者信息

Narducci Maria Lucia, Grasselli Annalisa, Biasucci Luigi Marzio, Farsetti Antonella, Mulè Antonino, Liuzzo Giovanna, La Torre Giuseppe, Niccoli Giampaolo, Mongiardo Rocco, Pontecorvi Alfredo, Crea Filippo

机构信息

Institute of Cardiology, Catholic University of Sacred Heart, Rome, Italy.

出版信息

J Am Coll Cardiol. 2007 Dec 18;50(25):2369-74. doi: 10.1016/j.jacc.2007.08.048.

Abstract

OBJECTIVES

We evaluated telomerase activity in circulating polymorphonuclear neutrophils (PMN) and in PMN isolated from coronary atherosclerotic plaques by a novel approach.

BACKGROUND

Delayed apoptosis of PMN have been demonstrated in unstable angina (UA). These cells have a finite lifespan with low telomerase activity, a polymerase that extends telomeres, structures essential for cell aging. Reactivation of telomerase has been associated with resistance to apoptosis.

METHODS

We studied 20 patients with UA and 6 patients with chronic stable angina (SA), undergoing a percutaneous coronary intervention. Circulating PMN were isolated from venous blood and PMN derived from coronary plaque were isolated from washing medium of angioplasty balloons.

RESULTS

Telomerase activity was higher in coronary plaque PMN of UA patients than in coronary plaque PMN of SA patients (122.7, range 20.5 to 3,696; and 47.7, range 16 to 212.6, respectively, p = 0.001) and higher than in peripheral PMN of SA patients (122.7, range 20.5 to 3,696 vs. 59, range 16.5 to 132.5, p = 0.001). We found a statistically significant difference between venous and coronary plaque PMN telomerase activity in UA patients (z = -2.875; p = 0.004). Among UA patients, a shorter time interval from symptom onset to coronary PMN sampling was the only independent predictor of high telomerase activity in coronary plaque PMN (p < 0.001, R2 = 0.75).

CONCLUSIONS

In UA patients, telomerase activity is high in coronary plaque PMN, while it is low in peripheral PMN. Telomerase reactivation in resident PMN resulting in a prolonged lifespan might play a key role in the early phases of instability.

摘要

目的

我们采用一种新方法评估了循环多形核中性粒细胞(PMN)以及从冠状动脉粥样硬化斑块中分离出的PMN中的端粒酶活性。

背景

已证实在不稳定型心绞痛(UA)中PMN凋亡延迟。这些细胞寿命有限,端粒酶活性低,端粒酶是一种延长端粒的聚合酶,端粒是细胞衰老所必需的结构。端粒酶的重新激活与抗凋亡有关。

方法

我们研究了20例接受经皮冠状动脉介入治疗的UA患者和6例慢性稳定型心绞痛(SA)患者。从静脉血中分离循环PMN,从血管成形术球囊的冲洗液中分离源自冠状动脉斑块的PMN。

结果

UA患者冠状动脉斑块PMN中的端粒酶活性高于SA患者冠状动脉斑块PMN中的端粒酶活性(分别为122.7,范围20.5至3696;和47.7,范围16至212.6,p = 0.001),且高于SA患者外周PMN中的端粒酶活性(122.7,范围20.5至3696对59,范围16.5至132.5,p = 0.001)。我们发现UA患者静脉和冠状动脉斑块PMN端粒酶活性之间存在统计学显著差异(z = -2.875;p = 0.004)。在UA患者中,从症状发作到冠状动脉PMN采样的时间间隔较短是冠状动脉斑块PMN中端粒酶活性高的唯一独立预测因素(p < 0.001,R2 = 0.75)。

结论

在UA患者中,冠状动脉斑块PMN中端粒酶活性高,而外周PMN中端粒酶活性低。驻留PMN中端粒酶重新激活导致寿命延长可能在不稳定的早期阶段起关键作用。

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