Gender and aging in a transgenic mouse model of hypertrophic cardiomyopathy
Gender and aging in a transgenic mouse model of hypertrophic cardiomyopathy
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DOI：
10.1152/ajpheart.2001.280.3.h1136
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发表时间：
2001-03-01
影响因子：
4.8
通讯作者：
Moore, RL
中科院分区：
文献类型：
--
作者：
Olsson, MC;Palmer, BM;Moore, RL
心肌肌球蛋白重链（MHC）突变可引起家族性肥厚性心肌病（FHC）。已经建立了一种转基因小鼠模型，其中在心脏中表达了错义（R403Q）等位基因和α -MHC中肌动蛋白结合缺失。我们采用等容左心制备方法研究转基因（TG）小鼠及其野生型（WT）幼崽心脏的收缩特性。雄性和雌性TG小鼠在4月龄时均出现左心室肥厚。年轻TG组左室肥厚伴左室舒张功能不全，左室收缩功能正常，男性异常。在10月龄时，雌性继续表现为左室同心性肥大，而雄性开始表现为左室扩张。雌性TG小鼠在10月龄时，左室舒张功能受损持续存在，没有收缩功能障碍的证据。相比之下，在10个月大的雄性TG小鼠中，左室舒张功能恶化，收缩功能受损。10个月大的TG组冠状动脉血流均减少。这些类型的改变可能导致肥厚性心肌病中典型的功能失代偿。总之，这些结果进一步强调了这种转基因小鼠模型在阐明FHC发病机制方面的潜在效用。
Mutations in the cardiac myosin heavy chain (MHC) can cause familial hypertrophic cardiomyopathy (FHC). A transgenic mouse model has been developed in which a missense (R403Q) allele and an actin-binding deletion in the alpha -MHC are expressed in the heart. We used an isovolumic left heart preparation to study the contractile characteristics of hearts from transgenic (TG) mice and their wild-type (WT) littermates. Both male and female TG mice developed left ventricular (LV) hypertrophy at 4 mo of age. LV hypertrophy was accompanied by LV diastolic dysfunction, but LV systolic function was normal and supranormal in the young TG females and males, respectively. At 10 mo of age, the females continued to present with LV concentric hypertrophy, whereas the males began to display LV dilation. In female TG mice at 10 mo of age, impaired LV diastolic function persisted without evidence of systolic dysfunction. In contrast, in 10-mo-old male TG mice, LV diastolic function worsened and systolic performance was impaired. Diminished coronary flow was observed in both 10-mo-old TG groups. These types of changes may contribute to the functional decompensation typically seen in hypertrophic cardiomyopathy. Collectively, these results further underscore the potential utility of this transgenic mouse model in elucidating pathogenesis of FHC.