Molecular genetic analyses of the CYP11B2 gene in cardiovascular tissues

除了醛固酮诱导钠和液体潴留的主要作用外，过量的醛固酮还具有直接的炎症和纤维化作用，有助于靶器官的退化，导致血管、肾脏和心脏炎症的发生；肝纤维化;和肥大。虽然肾上腺是醛固酮的主要来源，但在心肌肥大期间，醛固酮的产生和CYP11B2 mRNA编码水平在心室被诱导，而心脏本身合成醛固酮会导致心脏肥大。我们发现了DNA甲基化在CYP11B2基因抑制中的作用，并提出一种表观基因组机制可能与心脏病理生理中心脏醛固酮产生的增加有因果关系。同时，参与醛固酮生成的核受体（NGFIB, NURR1, NOR1, SF1）以组织特异性的方式差异地使用多个替代启动子（APs）。APs的使用在人的肾上腺和心血管组织中是不同的。

In addition to the primary effect of aldosterone to induce sodium and fluid retention, excess aldosterone has direct inflammatory and fibrotic effects contributing to target organ deterioration, leading to the development of vascular, renal, and cardiac inflammation ; fibrosis ; and hypertrophy. Although the adrenal gland is a major source of aldosterone, aldosterone production and levels of mRNA coding for CYP11B2 are induced in the ventricles during hypertrophy, and aldosterone synthesis from heart itself causes cardiac hypertrophy. We showed a role for DNA methylation in CYP11B2 gene repression and suggest an epigenomic mechanism may be causally linked with an increase in cardiac aldosterone production in the pathophysiology of the heart. Meanwhile, nuclear receptors(NGFIB, NURR1, NOR1, SF1) involved in aldosteronogenesis differentially employed multiple alternative promoters(APs) in a tissue-specific manner. The use of APs was different between human adrenal and cardiovascular tissues.