Elevated blood pressure and cardiac hypertrophy after ablation of the gly96/IEX-1 gene
Elevated blood pressure and cardiac hypertrophy after ablation of the gly96/IEX-1 gene
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DOI：
10.1152/japplphysiol.00306.2005
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发表时间：
2006-02-01
影响因子：
3.3
通讯作者：
Kumar, R
中科院分区：
文献类型：
--
作者：
Sommer, SL;Berndt, TJ;Kumar, R
Gly96/IEX-1是一种生长调节和凋亡调节的即刻早期基因，广泛表达于上皮和血管组织中。在血管组织中，该基因的表达是由机械拉伸诱导的，该基因的过表达可以防止损伤诱导的血管平滑肌肥大和新生内膜增生。我们现在发现，在小鼠中，Gly96/IEX-1基因的缺失与血压升高、心肌肥厚和左室短轴缩短率减少有关。清醒的雄性Gly96/IEX-1(-/-)小鼠的收缩压比Gly96/IEX-1(-/-)小鼠高20-25毫米汞柱。在Gly96/IEX-1(-/-)小鼠中，血清和/或尿钠、钾、肌酐、血管紧张素II、皮质酮、醛固酮、肾上腺素、去甲肾上腺素、前列腺素E-2、血栓素B-2、前列腺素-6-酮-1α、亚硝酸盐和硝酸盐、cAMP和cGMP浓度正常。饮食钠摄入量的改变不会改变Gly96/IEX-1(-/-)小鼠的血压。Gly96/IEX-1(-/-)小鼠的主动脉内皮型一氧化氮合酶、鸟苷环化酶-α和cGMP-1的mRNAs增加。N-奥米伽-硝基-L-精氨酸甲酯或L-精氨酸治疗不改变Gly96/IEX-1(-/-)小鼠的血压。Gly96/IEX-1(-/-)小鼠对注射硝普钠后血压下降的反应与野生型小鼠相似。与免疫功能异常的Gly96/IEX-1转基因小鼠相比，Gly96/IEX-1(-/-)小鼠具有正常的淋巴组织结构和淋巴组织中T和B细胞的正常补充。去除Gly96/IEX-1基因会导致高血压和心肌肥厚，提示该基因在心血管生理学中具有新的作用。
gly96/IEX 1 is a growth- and apoptosis-regulating, immediate early gene that is widely expressed in epithelial and vascular tissues. In vascular tissues, expression of the gene is induced by mechanical stretch, and overexpression of the gene prevents injury-induced vascular smooth muscle hypertrophy and neointimal hyperplasia. We now show that deletion of the gly96/ IEX-1 gene in mice is associated with development of elevated blood pressure, cardiac hypertrophy, and diminished fractional shortening of the left ventricle. Systolic blood pressure in conscious male gly96/ IEX-1(-/-) mice is 20-25 mmHg higher than in gly96/ IEX-1(-/-) mice. Serum and/ or urine concentrations of sodium, potassium, creatinine, angiotensin II, corticosterone, aldosterone, epinephrine, norepinephrine, prostaglandin E-2, thromboxane B-2, prostaglandin-6-keto-1 alpha, nitrites and nitrates, cAMP, and cGMP are normal in gly96/ IEX-1(-/-) mice. Alterations in dietary sodium intake do not alter blood pressure in gly96/ IEX-1(-/-) mice. Aortic mRNAs for endothelial nitric oxide synthase, guanylate cyclase-alpha, and cGMP kinase-1 are increased in gly96/ IEX-1(-/-) mice. Treatment with N-omega- nitro-L-arginine methyl ester or L-arginine does not alter blood pressure in gly96/ IEX-1(-/-) mice. Gly96/IEX-1(-/-) mice respond to infused sodium nitroprusside with decrements in blood pressure similar to those seen in wild-type littermate mice. In contrast to gly96/ IEX-1 transgenic mice that have abnormalities in immune function, gly96/ IEX-1(-/-) mice have normal lymphoid tissue architecture and a normal complement of T and B cells in lymphoid tissues. Ablation of the gly96/ IEX-1 gene results in hypertension and cardiac hypertrophy, suggesting a novel role for this gene in cardiovascular physiology.