Yamamuro Megumi, Yoshimura Michihiro, Nakayama Masafumi, Abe Koji, Sumida Hitoshi, Sugiyama Seigo, Saito Yoshihiko, Nakao Kazuwa, Yasue Hirofumi, Ogawa Hisao
Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Circ J. 2008 Aug;72(8):1346-50. doi: 10.1253/circj.72.1346.
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.
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 12 h. 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.
Aldosterone, but not angiotensin II, 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.
先前的一份报告显示，醛固酮可上调培养的新生大鼠心肌细胞中血管紧张素转换酶（ACE）的基因表达水平。ACE2是ACE的一种新型同源物，存在于人类心脏中，ACE2可将血管紧张素I转化为血管紧张素1-9，并将血管紧张素II转化为血管紧张素1-7，从而降低血管紧张素II水平。在本研究中，进行了一项调查，以观察醛固酮是否调节培养的新生大鼠心肌细胞中ACE2以及ACE的表达。
将原代新生大鼠心肌细胞与醛固酮一起培养。从这些心肌细胞中提取总RNA，并使用实时逆转录聚合酶链反应分析对ACE2、ACE和甘油醛-3-磷酸脱氢酶（GAPDH）的mRNA水平进行定量。醛固酮在12小时时显著降低ACE2 mRNA水平并增加ACE mRNA水平。然而，血管紧张素II对ACE2 mRNA水平或ACE mRNA水平均无影响。盐皮质激素受体拮抗剂依普利酮完全阻断了醛固酮导致的ACE mRNA水平升高和ACE2 mRNA水平降低。
醛固酮而非血管紧张素II通过盐皮质激素受体降低大鼠心肌细胞中ACE2 mRNA水平并增加ACE mRNA水平。醛固酮可能通过上调ACE和下调ACE2水平在心脏重塑中发挥重要作用。
