Diminished cardiac fibrosis in heart failure is associated with altered ventricular arrhythmia phenotype.
Diminished cardiac fibrosis in heart failure is associated with altered ventricular arrhythmia phenotype.
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DOI：
10.1111/j.1540-8167.2010.01736.x
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发表时间：
2010-09
影响因子：
2.7
通讯作者：
Naseem RH
中科院分区：
文献类型：
--
作者：
Massare J;Berry JM;Luo X;Rob F;Johnstone JL;Shelton JM;Bassel-Duby R;Hill JA;Naseem RH
我们试图确定间质纤维化在衰竭心室肌的促凋亡表型中的作用。在衰竭心室的病理性重构期间发生的多种细胞事件与室性心动过速（VT）的发生有关，包括间质纤维化。最近的研究表明，心室纤维化是可逆的，目前的抗重塑治疗减轻心室纤维化。然而，间质纤维化在衰竭心室肌的促炎表型中的作用目前还没有很好的定义。II类组蛋白脱乙酰基酶（HDAC）已经涉及促进胶原蛋白生物合成。由于这些酶受到蛋白激酶D1（PKD 1）的抑制，我们研究了心肌细胞特异性转基因过表达PKD 1组成型活性突变体（caPKD）的小鼠。将caPKD小鼠与通过严重胸主动脉缩窄（sTAB）诱导心肌病的动物进行比较。通过超声心动图和心电图方法分析心脏。间质纤维化通过组织学和生化定量进行评估。通过闭胸心内起搏诱导室性心律失常。在两种模型中观察到相似程度的肥大性生长、收缩功能障碍和死亡率。在sTAB小鼠中，很容易检测到强烈的心室纤维化，但在caPKD小鼠中心肌胶原蛋白含量显著降低。正如预期的那样，VT在sTAB小鼠中容易通过程序刺激诱导，而VT在caPKD小鼠中诱导性较低。令人惊讶的是，VT发作在caPKD小鼠中表现出更长的周期长度和更长的持续时间。心室纤维化减轻与VT诱导减少、VT持续时间增加和心律失常周期长度显著延长相关。
We sought to define the role of interstitial fibrosis in the proarrhythmic phenotype of failing ventricular myocardium. Multiple cellular events that occur during pathological remodeling of the failing ventricle are implicated in the genesis of ventricular tachycardia (VT), including interstitial fibrosis. Recent studies suggest that ventricular fibrosis is reversible, and current anti-remodeling therapies attenuate ventricular fibrosis. However, the role of interstitial fibrosis in the proarrhythmic phenotype of failing ventricular myocardium is currently not well defined. Class II histone deacetylases (HDACs) have been implicated in promoting collagen biosynthesis. As these enzymes are inhibited by protein kinase D1 (PKD1), we studied mice with cardiomyocyte-specific transgenic over-expression of a constitutively activemutant of PKD1 (caPKD). caPKD mice were compared with animals in which cardiomyopathy was induced by severe thoracic aortic banding (sTAB). Hearts were analyzed by echocardiographic and electrocardiographic means. Interstitial fibrosis was assessed by histology and quantified biochemically. Ventricular arrhythmias were induced by closed-chest, intracardiac pacing. Similar degrees of hypertrophic growth, systolic dysfunction and mortality were observed in the two models. In sTAB mice, robust ventricular fibrosis was readily detected, but myocardial collagen content was significantly reduced in caPKD mice. As expected, VT was readily inducible by programmed stimulation in sTAB mice and VT was less inducible in caPKD mice. Surprisingly, episodes of VT manifested longer cycle lengths and longer duration in caPKD mice. Attenuated ventricular fibrosis is associated with reduced VT inducibility, increased VT duration, and significantly longer arrhythmia cycle length.
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影响因子：
8.3
作者：
Petrov, VV;Fagard, RH;Lijnen, PJ
通讯作者：
Lijnen, PJ
影响因子：
4.6
作者：
Maguire, CT;Wakimoto, H;Berul, CI
通讯作者：
Berul, CI
影响因子：
10.8
作者：
Maturana, Andres D.;Waelchli, Sebastien;Kuroda, Shun'ichi
通讯作者：
Kuroda, Shun'ichi
DOI：
10.1111/j.1540-8159.1997.tb06199.x
发表时间：
1997-02-01
影响因子：
1.8
作者：
Spach, MS;Boineau, JP
通讯作者：
Boineau, JP
影响因子：
5.3
作者：
Harrison, Brooke C.;Kim, Mi-Sung;McKinsey, Timothy A.
通讯作者：
McKinsey, Timothy A.