Study of Cardiac Steroidogenesis

心脏类固醇生成的研究

基本信息

批准号：
15390249
负责人：
YOSHIMURA Michihiro
金额：
$ 9.02万
依托单位：
Kumamoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15390249/
关键词：
aldosterone dehydroepiandrosterone ACTH Heart Failure Hypertension ACE ACE2 Angiotensin II コルチゾール CYP17 CYP11B1 CYP11B2 冠静脈洞

项目摘要

In heart failure or hypertension, it has come to seem that not only circulating aldosterone but also tissue aldosterone has some pathophysiological meanings. In our laboratory, we continuously examined the study of cardiac Steroidogenesis and the relating hormones in humans. In our recently study, we found that aldosterone is secreted from the failing heart ; on the other hand, dehydroepiandrosterone(DHEA) is secreted from the control(healthy) heart in humans(Circulation 2004). In a sense, when the heart is healthy, it has the feature as zona reticularis of the adrenal gland ; however, when the heart condition is deteriorated, it appears the feature of zona glomerulosa. It is interesting to see the switching of the cascades to produce aldosterone or DHEA in relation to the heart conditions ; this is our big challenge of overlapping the concepts of the heart and the adrenal gland.Furthermore, we recently clarified the ACTH secretion from the hearts(ventricles) of patients with hypertens … More ion(J Hypertens 2005). The amount of ACTH secreted from the ventricle was significantly correlated with the grade of blood pressure, suggesting a certain participation of cardiac ACTH to the pathophysiology of essential hypertension. Moreover, there was a positive correlation between cardiac ACTH secretion and cardiac aldosterone secretion, suggesting that, unlike the adrenal gland, ACTH may continue promoting synthesis of aldosterone in the heart. Thus, a new concept called cardiac Hypothalamus-Pituitary-Adrenal(HPA) system study was established in addition to the cardiac RAA system study.Previously, we reported that aldosterone induces the gene expression of angiotensin-converting enzyme(ACE). On the other hand, we found a new action of aldosterone as for the inhibition of the ACE2 gene expression, which was via the mineralocorticoid receptor(MR). Augmentation of the ACE gene expression and inhibition of the ACE2 gene expression by aldosterone would contribute to the deformation of Angiotensin_<1-7> and formation of Angiotensin II, leading to worsening heart failure. Less

在心力衰竭或高血压中，似乎不仅循环醛固酮而且组织醛固酮也具有某些病理生理学意义。在我们的实验室中，我们不断研究人类心脏类固醇生成和相关激素。发现醛固酮是从衰竭的心脏分泌的；另一方面，脱氢表雄酮（DHEA）是从人类控制（健康）的心脏（循环系统）分泌的。 2004）。从某种意义上说，当心脏健康时，它具有肾上腺网状带的特征；然而，当心脏状况恶化时，它会出现肾小球带的特征，这是很有趣的。产生与心脏病相关的醛固酮或 DHEA 的级联；这是我们重叠心脏和肾上腺概念的巨大挑战。此外，我们最近阐明了高血压患者心脏（心室）ACTH的分泌情况（J Hypertens 2005），心室分泌的ACTH量与血压等级显着相关，提示心脏ACTH对血压的影响有一定的参与。此外，心脏 ACTH 分泌与心脏醛固酮分泌之间存在正相关性，这表明与肾上腺不同，ACTH 可能会继续促进合成。因此，除了心脏RAA系统研究之外，还建立了一个新的概念，即心脏下丘脑-垂体-肾上腺(HPA)系统研究。此前，我们报道了醛固酮诱导血管紧张素转换酶(ACE)基因的表达。另一方面，我们发现醛固酮抑制ACE2基因表达的新作用是通过盐皮质激素受体（MR）实现的。醛固酮增强ACE基因表达和抑制ACE2基因表达会导致血管紧张素_<1-7>变形和血管紧张素II形成，导致心力衰竭恶化。

项目成果

期刊论文数量（17）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Ito T, et al.: "Inhibitory effect of natriuretic peptides on aldosterone synthase gene expression in cultured neonatal rat cardiocytes"Circulation. 107. 807-810 (2003)

Ito T 等人：“利钠肽对培养的新生大鼠心肌细胞中醛固酮合酶基因表达的抑制作用”循环。

DOI：
发表时间：
期刊：
影响因子：
0
作者：
通讯作者：

Adrenocorticotropic hormone (ACTH) is produced in the ventricle of patients with essential hypertension

原发性高血压患者的心室产生促肾上腺皮质激素（ACTH）

DOI：
发表时间：
2005
期刊：
J Hypertens 23(2)
影响因子：
0
作者：
Mizuno Y;et al.
通讯作者：
et al.

Plasma levels of B-type natriuretic peptide as a prognostic marker after acute myocardial infarction : a long-time follow-up analysis.

B 型利尿钠肽的血浆水平作为急性心肌梗死后的预后标志物：长期随访分析。

DOI：
发表时间：
2004
期刊：
Circulation 110(11)
影响因子：
0
作者：
Suzuki S;Yoshimura M;Nakayama M;Mizuno Y;Ito T;Nakamura S;Abe K;Yamamoto M;Sakamoto T;Saito Y;Nakao K;Yasue H;Ogawa H.
通讯作者：
Ogawa H.

Methods in molecular medicine