Knockout of β1- and β2-adrenoceptors attenuates pressure overload-induced cardiac hypertrophy and fibrosis
Knockout of β1- and β2-adrenoceptors attenuates pressure overload-induced cardiac hypertrophy and fibrosis
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DOI：
10.1038/sj.bjp.0707622
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发表时间：
2008-02-01
影响因子：
7.3
通讯作者：
Du, X-J
中科院分区：
文献类型：
--
作者：
Kiriazis, H.;Wang, K.;Du, X-J
背景和目的：β-肾上腺素受体在心脏病中的作用仍存在争议。虽然β受体阻滞剂改善了心脏病的进展，但其机制仍不明确。我们使用β（1）和β（2）肾上腺素受体敲除小鼠和野生型（WT）小鼠研究了β-肾上腺素受体对心脏肥大生长的影响。实验方法：小鼠进行主动脉结扎或假手术，通过超声心动图和微测压测定其心脏功能。关键结果：主动脉结扎后4周和12周，左心室：相对于假手术组，野生型小鼠的体重比增加了80-87%，但敲除小鼠的体重比仅增加了15%。尽管肥大性生长减弱，但敲除小鼠的心室功能得以维持。WT小鼠对压力超负荷的反应是炎性细胞因子和纤维化生长因子的基因表达上调，并伴有严重的心脏纤维化。所有这些影响是不存在的基因敲除animals.Conclusion和影响：我们的研究结果显着衰减的心脏肥大和纤维化后，压力超负荷在此敲除模型强调，β-肾上腺素能受体信号传导起着核心作用，心脏肥大和适应不良后压力超负荷。
Background and purpose: The role of beta-adrenoceptors in heart disease remains controversial. Although beta-blockers ameliorate the progression of heart disease, the mechanism remains undefined. We investigated the effect of b-adrenoceptors on cardiac hypertrophic growth using beta(1)- and beta(2)-adrenoreceptor knockout and wild-type (WT) mice.Experimental approach: Mice were subjected to aortic banding or sham surgery, and their cardiac function was determined by echocardiography and micromanometry.Key results: At 4 and 12 weeks after aortic banding, the left ventricle: body mass ratio was increased by 80-87% in wild-type mice, but only by 15% in knockouts, relative to sham-operated groups. Despite the blunted hypertrophic growth, ventricular function in knockouts was maintained. WT mice responded to pressure overload with up-regulation of gene expression of inflammatory cytokines and fibrogenic growth factors, and with severe cardiac fibrosis. All these effects were absent in the knockout animals.Conclusion and implications: Our findings of a markedly attenuated cardiac hypertrophy and fibrosis following pressure overload in this knockout model emphasize that beta-adrenoceptor signalling plays a central role in cardiac hypertrophy and maladaptation following pressure overload.