Cardiac response to pressure overload in 129S1/SvImJ and C57BL/6J mice: temporal- and background-dependent development of concentric left ventricular hypertrophy
Cardiac response to pressure overload in 129S1/SvImJ and C57BL/6J mice: temporal- and background-dependent development of concentric left ventricular hypertrophy
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DOI：
10.1152/ajpheart.00816.2006
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发表时间：
2007-05-01
影响因子：
4.8
通讯作者：
Threadgill, David W.
中科院分区：
文献类型：
--
作者：
Barrick, Cordelia J.;Rojas, Mauricio;Threadgill, David W.
左心室肥厚 (LVH) 是心血管疾病发病和死亡的危险因素，通常由原发性高血压引起。高血压可诱发 LVH 的三种几何模式：向心重塑、向心肥大和离心肥大。临床研究表明，不同的潜在病因、基因修饰和死亡风险与 LVH 几何模式相关。由于压力过载引起的 LVH 可以使用横主动脉缩窄 (TAC) 进行实验建模，并且通常使用具有不同基线心血管表型的 C57BL/6J (B6) 和 129S1/SvImJ (129S1) 菌株，因此我们进行了系列超声心动图研究，以评估男性 B6、129S1 和 8 周 TAC 后的心功能。 B6129F1 (H) 小鼠。 B6 小鼠发病较早，收缩功能受损更明显，伴有相应的左心室和右心室扩张、纤维化、肥大标志物表达变化以及 TAC 后 5 周肝脏重量增加。这些观察结果表明，B6 小鼠患有偏心肥大，伴有收缩功能障碍和右侧心力衰竭。相比之下，我们发现 129S1 和 F1 小鼠延迟向失代偿性心力衰竭的转变，其中 129S1 小鼠在 TAC 后 8 周之前表现出保留的收缩功能，并且在 TAC 后 5 周时组织学和肥大标记物发生相对轻微的变化。与向心肥大一致，我们的结果表明，这些菌株以时间依赖性方式对压力超负荷表现出不同的心脏反应，并且对初始向心肥大的遗传易感性对偏心肥大占主导地位。这些结果还意味着，当使用混合遗传背景时，遗传背景差异可能会使 TAC 研究的解释变得复杂。
Left ventricular hypertrophy (LVH), a risk factor for cardiovascular morbidity and mortality, is commonly caused by essential hypertension. Three geometric patterns of LVH can be induced by hypertension: concentric remodeling, concentric hypertrophy, and eccentric hypertrophy. Clinical studies suggest that different underlying etiologies, genetic modifiers, and risk of mortality are associated with LVH geometric patterns. Since pressure overload-induced LVH can be modeled experimentally using transverse aortic constriction (TAC) and since C57BL/6J (B6) and 129S1/SvImJ (129S1) strains, which have different baseline cardiovascular phenotypes, are commonly used, we conducted serial echo-cardiographic studies to assess cardiac function up to 8 wk of post-TAC in male B6, 129S1, and B6129F1 (H) mice. B6 mice had an earlier onset and more pronounced impairment in contractile function, with corresponding left and right ventricular dilatation, fibrosis, change in expression of hypertrophy marker, and increased liver weights at 5 wk of post-TAC. These observations suggest that B6 mice had eccentric hypertrophy with systolic dysfunction and right-sided heart failure. In contrast, we found that 129S1 and F1 mice delayed transition to decompensated heart failure, with 129S1 mice exhibiting preserved systolic function until 8 wk of post-TAC and relatively mild alterations in histology and markers of hypertrophy at 5 wk post-TAC. Consistent with concentric hypertrophy, our results show that these strains manifest different cardiac responses to pressure overload in a time-dependent manner and that genetic susceptibility to initial concentric hypertrophy is dominant to eccentric hypertrophy. These results also imply that genetic background differences can complicate interpretation of TAC studies when using mixed genetic backgrounds.