Aldosterone, but not angiotensin II, reduces angiotensin converting enzyme 2 gene expression levels in cultured neonatal rat cardiomyocytes
Aldosterone, but not angiotensin II, reduces angiotensin converting enzyme 2 gene expression levels in cultured neonatal rat cardiomyocytes
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DOI：
10.1253/circj.72.1346
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发表时间：
2008-08-01
影响因子：
3.3
通讯作者：
Ogawa, Hisao
中科院分区：
文献类型：
--
作者：
Yamamuro, Megumi;Yoshimura, Michihiro;Ogawa, Hisao
背景先前有报道表明，醛固酮可上调培养新生大鼠心肌细胞血管紧张素转换酶（ACE）基因表达水平。ACE2是一种新的ACE同源物，存在于人的心脏中，ACE2将血管紧张素I转化为血管紧张素1-9，将血管紧张素II转化为血管紧张素1-7，从而降低血管紧张素II的水平。在本研究中，我们研究了醛固酮是否调节培养的新生大鼠心肌细胞中ACE2和ACE的表达。方法与结果用醛固酮培养初生大鼠心肌细胞。提取心肌细胞总RNA，采用实时逆转录聚合酶链式反应法定量测定ACE2、ACE和GAPDH mRNA水平。醛固酮显著降低12h时ACE2 mRNA水平，提高12h时ACE mRNA水平。然而，血管紧张素II对ACE2 mRNA水平和ACE mRNA水平均无影响。矿化皮质激素受体拮抗剂Eplerenone完全阻断醛固酮引起的ACE mRNA水平升高和ACE2 mRNA水平降低。结论醛固酮可通过矿化皮质激素受体降低大鼠心肌细胞ACE2 mRNA水平，而血管紧张素H可通过矿化皮质激素受体提高心肌细胞ACE2 mRNA水平。醛固酮可能通过上调ACE和下调ACE2水平在心脏重构中发挥重要作用。
Background A previous report showed that aldosterone upregulates angiotensin converting enzyme (ACE) gene expression levels in cultured neonatal rat cardiocytes. ACE2 is a novel homologue of ACE, which exists in the human heart, and ACE2 converts angiotensin I to angiotensin 1-9 and angiotensin II to angiotensin 1-7, thereby decreasing angiotensin II levels. In the present study, an investigation took place to see whether aldosterone regulates the expression of ACE2 as well as that of ACE in cultured neonatal rat cardiomyocytes.Methods and Results Primary neonatal rat cardiomyocytes were cultured with aldosterone. Total RNA was extracted from these cardiomyocytes and quantified the mRNA levels of ACE2, ACE and GAPDH by using real-time reverse transcription polymerase chain reaction analysis. Aldosterone significantly decreased ACE2 mRNA levels and increased ACE mRNA levels at 12h. Angiotensin II, however, had no effect on either ACE2 mRNA levels or ACE mRNA levels. Eplerenone, a mineralocorticoid receptor antagonist, completely blocked the increase in ACE mRNA levels and the reduction in ACE2 mRNA levels due to aldosterone.Conclusion Aldosterone, but not angiotensin H, reduced ACE2 mRNA levels and increased ACE mRNA levels in rat cardiomyocytes via mineralocorticoid receptor. Aldosterone might play an important role in cardiac remodeling by upregulating ACE and downregulating ACE2 levels.