Pleiotropic effects of neutrophils on myocyte apoptosis and left ventricular remodeling during early volume overload.
Pleiotropic effects of neutrophils on myocyte apoptosis and left ventricular remodeling during early volume overload.
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DOI：
10.1016/j.yjmcc.2009.08.016
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发表时间：
2009-11
影响因子：
5
通讯作者：
Sabri, Abdelkarim
中科院分区：
文献类型：
--
作者：
Kolpakov, Mikhail A.;Seqqat, Rachid;Rafiq, Khadija;Xi, Hang;Margulies, Kennneth B.;Libonati, Joseph R.;Powel, Pamela;Houser, Steven R.;Dell'italia, Louis J.;Sabri, Abdelkarim
中性粒细胞在病理性心脏重构中的作用的现有证据大多与急性心肌梗死后有关。然而，中性粒细胞是否直接参与急性心肌梗死以外事件后心脏重塑的发病机制仍不清楚。在这里，我们表明，急性离心性肥大引起的腹主动脉-腔静脉瘘（ACF）在大鼠引起的炎症反应的增加，其特征在于激活的STAT通路和增加的中性粒细胞在心肌中的浸润。这种早期炎症与间质胶原积聚减少和肌细胞凋亡增加有关。中性粒细胞浸润阻断剂在24小时时减弱了ACF诱导的MMP活化、ECM降解和心肌细胞凋亡，并在2周和3周时减弱了ACF诱导的离心性肥大的发展，表明中性粒细胞与ACF诱导的心脏重塑之间存在因果关系。相反，持续4周以上的中性粒细胞耗竭导致不利的心脏重塑，心脏扩张和巨噬细胞浸润进一步增加，但心肌细胞凋亡水平没有变化。这些数据支持中性粒细胞在MMP激活、ECM降解和心肌细胞凋亡中的功能作用，并强调慢性抗中性粒细胞治疗对早期VO诱导的心脏重塑的不良影响。
Most of the available evidence on the role of neutrophils on pathological cardiac remodeling has been pertained after acute myocardial infarction. However, whether neutrophils directly contribute to the pathogenesis of cardiac remodeling after events other than acute myocardial infarction remains unknown. Here we show that acute eccentric hypertrophy induced by aorto-caval fistula (ACF) in the rats induced an increase in the inflammatory response characterized by activation of the STAT pathway and increased infiltration of neutrophils in the myocardium. This early inflammation was associated with a decrease in interstitial collagen accumulation and an increase in myocyte apoptosis. Neutrophil infiltration blockade attenuated MMP activation, ECM degradation, and myocyte apoptosis induced by ACF at 24hrs and attenuated the development of eccentric hypertrophy induced by ACF at 2- and 3-weeks, suggesting a causal relationship between neutrophils and the ACF-induced cardiac remodeling. In contrast, sustained neutrophil depletion over 4-weeks resulted in adverse cardiac remodeling with further increase in cardiac dilatation and macrophage infiltration, but with no change in myocyte apoptosis level. These data support a functional role for neutrophils in MMP activation, ECM degradation, and myocyte apoptosis during eccentric cardiac hypertrophy and underscore the adverse effects of chronic anti-neutrophil therapy on cardiac remodeling induced by early VO.
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DOI：
10.1358/mf.2002.24.7.696541
发表时间：
2002-09-01
影响因子：
--
作者：
Dun, Y;Zhi, JM;Zhao, ZQ
通讯作者：
Zhao, ZQ
影响因子：
4.8
作者：
Rafiq, Khadija;Kolpakov, Mikhail A.;Sabri, Abdelkarim
通讯作者：
Sabri, Abdelkarim
影响因子：
5.5
作者：
SEKIYA, S;GOTOH, S;SENDO, F
通讯作者：
SENDO, F
影响因子：
4.8
作者：
SIMPSON, PJ;MITSOS, SE;LUCCHESI, BR
通讯作者：
LUCCHESI, BR
影响因子：
37.8
作者：
Maron, BJ;Towbin, JA;Young, JB
通讯作者：
Young, JB