Cardiac myocyte-specific excision of the β1 integrin gene results in myocardial fibrosis and cardiac failure
Cardiac myocyte-specific excision of the β1 integrin gene results in myocardial fibrosis and cardiac failure
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DOI：
10.1161/hh0402.105790
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发表时间：
2002-03-08
影响因子：
20.1
通讯作者：
Ross, RS
中科院分区：
文献类型：
--
作者：
Shai, SY;Harpf, AE;Ross, RS
整合素连接细胞外基质和细胞骨架，在细胞生长、分化、迁移中起重要作用。和生存所有鼠组织中β 1整联蛋白的消融导致围植入期胚胎死亡。为了研究β 1整合素在心肌中的作用，我们使用Cre-LoxP技术在心室肌细胞中特异性地表达β 1整合素基因。心室肌细胞β 1整联蛋白基因切除纯合子的动物出生在适当的数量和成长到成年。这些动物的心脏中β ID整联蛋白的对照水平为18%，并显示心肌纤维化。与对照组相比，5周龄完整β 1整合素基因敲除小鼠的高保真微压计导管显示左心室基础和多巴酚丁胺刺激的收缩和舒张（LV dP/dt（max）和LV dP/dt（min））降低（每组n = 8 - 10，P
Integrins link the extracellular matrix to the cellular cytoskeleton and serve important roles in cell growth, differentiation, migration. and survival. Ablation of beta1 integrin in all murine tissues results in peri-implantation embryonic lethality. To investigate the role of beta1 integrin in the myocardium, we used Cre-LoxP technology to inactivate the beta1 integrin gene exclusively in ventricular cardiac myocytes. Animals with homozygous ventricular myocyte beta1 integrin gene excision were born in appropriate numbers and grew into adulthood. These animals had 18% of control levels of betaID integrin protein in the heart and displayed myocardial fibrosis. High-fidelity micromanometer-tipped catheterization of the intact 5-week-old beta1 integrin knockout mice showed depressed left ventricular basal and dobutamine-stimulated contractility and relaxation (LV dP/dt(max) and LV dP/dt(min)) as compared with control groups (n = 8 to 10 of each, P