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人类外周血单核细胞亚群异质性对原发性急性心肌梗死患者心肌挽救的影响。

Impact of heterogeneity of human peripheral blood monocyte subsets on myocardial salvage in patients with primary acute myocardial infarction.

作者信息

Tsujioka Hiroto, Imanishi Toshio, Ikejima Hideyuki, Kuroi Akio, Takarada Shigeho, Tanimoto Takashi, Kitabata Hironori, Okochi Keishi, Arita Yu, Ishibashi Kohei, Komukai Kenichi, Kataiwa Hideaki, Nakamura Nobuo, Hirata Kumiko, Tanaka Atsuhsi, Akasaka Takashi

机构信息

Department of Cardiovascular Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama City, Wakayama, Japan.

出版信息

J Am Coll Cardiol. 2009 Jul 7;54(2):130-8. doi: 10.1016/j.jacc.2009.04.021.

Abstract

OBJECTIVES

We examined whether distinct monocyte subsets contribute in specific ways to myocardial salvage in patients with acute myocardial infarction (AMI).

BACKGROUND

Recent studies have shown that monocytes in human peripheral blood are heterogeneous.

METHODS

We studied 36 patients with primary AMI. Peripheral blood sampling was performed 1, 2, 3, 4, 5, 8, and 12 days after AMI onset. Two monocyte subsets (CD14(+)CD16(-) and CD14(+)CD16(+)) were measured by flow cytometry. The extent of myocardial salvage 7 days after AMI was evaluated by cardiovascular magnetic resonance imaging as the difference between myocardium at risk (T2-weighted hyperintense lesion) and myocardial necrosis (delayed gadolinium enhancement). Cardiovascular magnetic resonance imaging was also performed 6 months after AMI.

RESULTS

Circulating CD14(+)CD16(-) and CD14(+)CD16(+) monocytes increased in AMI patients, peaking on days 3 and 5 after onset, respectively. Importantly, the peak levels of CD14(+)CD16(-) monocytes, but not those of CD14(+)CD16(+) monocytes, were significantly negatively associated with the extent of myocardial salvage. We also found that the peak levels of CD14(+)CD16(-) monocytes, but not those of CD14(+)CD16(+) monocytes, were negatively correlated with recovery of left ventricular ejection fraction 6 months after infarction.

CONCLUSIONS

The peak levels of CD14(+)CD16(-) monocytes affect both the extent of myocardial salvage and the recovery of left ventricular function after AMI, indicating that the manipulation of monocyte heterogeneity could be a novel therapeutic target for salvaging ischemic damage.

摘要

目的

我们研究了不同的单核细胞亚群是否以特定方式对急性心肌梗死(AMI)患者的心肌挽救有影响。

背景

最近的研究表明,人类外周血中的单核细胞具有异质性。

方法

我们研究了36例原发性AMI患者。在AMI发病后1、2、3、4、5、8和12天进行外周血采样。通过流式细胞术检测两个单核细胞亚群(CD14(+)CD16(-)和CD14(+)CD16(+))。通过心血管磁共振成像评估AMI后7天的心肌挽救程度,即危险心肌(T2加权高信号病变)与心肌坏死(延迟钆增强)之间的差异。AMI后6个月也进行了心血管磁共振成像检查。

结果

AMI患者循环中的CD14(+)CD16(-)和CD14(+)CD16(+)单核细胞增加,分别在发病后第3天和第5天达到峰值。重要的是,CD14(+)CD16(-)单核细胞的峰值水平与心肌挽救程度显著负相关,而CD14(+)CD16(+)单核细胞的峰值水平则无此相关性。我们还发现,CD14(+)CD16(-)单核细胞的峰值水平与梗死后6个月左心室射血分数的恢复呈负相关,而CD14(+)CD16(+)单核细胞的峰值水平则无此相关性。

结论

CD14(+)CD16(-)单核细胞的峰值水平影响AMI后的心肌挽救程度和左心室功能恢复,表明操纵单核细胞异质性可能是挽救缺血损伤的新治疗靶点。

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