Intravenous and intramyocardial injection of apoptotic white blood cell suspensions prevents ventricular remodelling by increasing elastin expression in cardiac scar tissue after myocardial infarction.
Intravenous and intramyocardial injection of apoptotic white blood cell suspensions prevents ventricular remodelling by increasing elastin expression in cardiac scar tissue after myocardial infarction.
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凋亡和心脏内注射凋亡白细胞悬浮液可通过在心肌梗塞后增加心脏疤痕组织中的弹性蛋白表达来防止心室重塑。
DOI：
10.1007/s00395-011-0173-0
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发表时间：
2011-06
影响因子：
9.5
通讯作者：
Ankersmit HJ
中科院分区：
文献类型：
--
作者：
Lichtenauer M;Mildner M;Baumgartner A;Hasun M;Werba G;Beer L;Altmann P;Roth G;Gyöngyösi M;Podesser BK;Ankersmit HJ
急性心肌梗死（AMI）后发生的充血性心力衰竭是发病和死亡的主要原因。 AMI 后基于细胞的治疗的临床试验证明仅具有中等益处。我们之前可以证明，凋亡外周血单核细胞 (PBMC) 的悬浮液能够减少 AMI 大鼠模型的心肌损伤。在这里，我们通过实验研究了 AMI 后预防心室重构和保护心脏功能所涉及的生化机制。大鼠冠状动脉结扎诱发实验性AMI后，静脉内或心肌内注射凋亡细胞的细胞悬液。施用细胞培养基或活PBMC作为对照。进行免疫组织学分析以分析缺血心肌中的细胞浸润。通过超声心动图对心脏功能进行量化。梗塞心脏的面积测量显示，用凋亡的 PBMC 悬浮液（静脉内或心肌内注射）治疗的大鼠中，梗塞面积显着减小，AMI 后重塑得到改善。此外，与对照组相比，这些心脏的巨噬细胞和 c-kit、FLK-1、IGF-I 和 FGF-2 染色阳性细胞的归巢能力增强。这项研究的一个主要发现是，在注射凋亡细胞的大鼠中，疤痕组织内弹性纤维和胶原纤维的比例以有利的方式改变。静脉内或心肌内注射凋亡细胞悬浮液可减弱实验性 AMI 后的心肌重塑，保留左心室功能，增加再生细胞的归巢并改变心脏疤痕组织的组成。弹性纤维的较高表达为心脏疤痕组织提供被动能量，从而预防心室重塑。本文的在线版本 (doi:10.1007/s00395-011-0173-0) 包含补充材料，可供授权用户使用。
Congestive heart failure developing after acute myocardial infarction (AMI) is a major cause of morbidity and mortality. Clinical trials of cell-based therapy after AMI evidenced only a moderate benefit. We could show previously that suspensions of apoptotic peripheral blood mononuclear cells (PBMC) are able to reduce myocardial damage in a rat model of AMI. Here we experimentally examined the biochemical mechanisms involved in preventing ventricular remodelling and preserving cardiac function after AMI. Cell suspensions of apoptotic cells were injected intravenously or intramyocardially after experimental AMI induced by coronary artery ligation in rats. Administration of cell culture medium or viable PBMC served as controls. Immunohistological analysis was performed to analyse the cellular infiltrate in the ischaemic myocardium. Cardiac function was quantified by echocardiography. Planimetry of the infarcted hearts showed a significant reduction of infarction size and an improvement of post AMI remodelling in rats treated with suspensions of apoptotic PBMC (injected either intravenously or intramoycardially). Moreover, these hearts evidenced enhanced homing of macrophages and cells staining positive for c-kit, FLK-1, IGF-I and FGF-2 as compared to controls. A major finding in this study further was that the ratio of elastic and collagenous fibres within the scar tissue was altered in a favourable fashion in rats injected with apoptotic cells. Intravenous or intramyocardial injection of apoptotic cell suspensions results in attenuation of myocardial remodelling after experimental AMI, preserves left ventricular function, increases homing of regenerative cells and alters the composition of cardiac scar tissue. The higher expression of elastic fibres provides passive energy to the cardiac scar tissue and results in prevention of ventricular remodelling. The online version of this article (doi:10.1007/s00395-011-0173-0) contains supplementary material, which is available to authorized users.
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DOI：
10.1111/j.1365-2362.2009.02111.x
发表时间：
2009-06-01
影响因子：
5.5
作者：
Ankersmit, H. J.;Hoetzenecker, K.;Podesser, B. K.
通讯作者：
Podesser, B. K.
影响因子：
4
作者：
Kadl, A;Huber, J;Leitinger, N
通讯作者：
Leitinger, N
影响因子：
4
作者：
Matthews, KG;Devlin, GP;Bass, JJ
通讯作者：
Bass, JJ
影响因子：
37.8
作者：
Cimini, Massimo;Fazel, Shafie;Li, Ren-Ke
通讯作者：
Li, Ren-Ke
影响因子：
10.8
作者：
Moellmann, Helge;Nef, Holger M.;Elsaesser, Albrecht
通讯作者：
Elsaesser, Albrecht