Direct, convergent hypersensitivity of calcium-activated force generation produced by hypertrophic cardiomyopathy mutant α-tropomyosins in adult cardiac myocytes
Direct, convergent hypersensitivity of calcium-activated force generation produced by hypertrophic cardiomyopathy mutant α-tropomyosins in adult cardiac myocytes
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成人心肌细胞中肥厚型心肌病突变体 α-原肌球蛋白产生的钙激活力产生的直接、会聚超敏反应
DOI：
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发表时间：
1999
期刊：
影响因子：
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通讯作者：
J. Metzger
中科院分区：
文献类型：
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作者：
D. Michele;F. Albayya;J. Metzger
家族性肥厚性心肌病是一种临床上和遗传上多样的常染色体显性遗传病，在缺乏已知肥厚性刺激的情况下，以心室肥大和心肌细胞紊乱为特征。它与许多心脏收缩蛋白有关，包括α-原肌球蛋白（Tm）的四点突变。在这里，我们使用腺病毒介导的基因转移到体外成人心肌细胞中，结果表明，在培养5-6天后，所有四种肥厚性心肌病α-Tm蛋白都可以表达并结合到心肌细胞的正常肉瘤结构中，其水平与正常α-Tm蛋白相似。单个心肌细胞的等长力记录显示，在钙浓度低于最大值时，力输出不适当增加，具有特定的突变等位基因等级。这些数据表明α-Tm突变的直接钙致敏作用的严重程度可以预测α-Tm突变相关肥厚性心肌病的临床严重程度。
Familial hypertrophic cardiomyopathy is a clinically and genetically diverse autosomal dominant disorder characterized by ventricular hypertrophy and myocyte disarray in the absence of known hypertrophic stimuli. It has been linked to many cardiac contractile proteins, including four point mutations in α-tropomyosin (Tm). Here we use adenoviral-mediated gene transfer into adult cardiac myocytes in vitro to show that all four hypertrophic cardiomyopathy α-Tm proteins can be expressed and incorporated into normal sarcomeric structures in cardiac myocytes at similar levels as normal α-Tm proteins after 5–6 days in culture. Isometric force recordings of single cardiac myocytes demonstrated inappropriate increased force output at submaximal calcium concentration with a specific mutant allele hierarchy. These data indicate that the severity of direct calcium-sensitizing effect of mutations in α-Tm may predict the clinical severity of mutant α-Tm-associated hypertrophic cardiomyopathy.
影响因子：
158.5
作者：
WATKINS, H;ROSENZWEIG, A;SEIDMAN, JG
通讯作者：
SEIDMAN, JG
α-原肌球蛋白突变的家族性肥厚型心肌病小鼠模型表现出心脏功能障碍。
影响因子：
20.1
作者：
Muthuchamy,M;Pieples,K;Rethinasamy,P;Hoit,B;Grupp,IL;Boivin,GP;Wolska,B;Evans,C;Solaro,RJ;Wieczorek,DF
通讯作者：
Wieczorek,DF
家族性肥厚型心肌病基因座定位于染色体 15q2。
DOI：
10.1073/pnas.90.13.6270
发表时间：
1993
影响因子：
11.1
作者：
Thierfelder,L;MacRae,C;Watkins,H;Tomfohrde,J;Williams,M;McKenna,W;Bohm,K;Noeske,G;Schlepper,M;Bowcock,A
通讯作者：
Bowcock,A