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| 1.
論文 |
論文
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Demura, Masashi ; Wang, Fen ; Yoneda, Takashi ; Karashima, Shigehiro ; Mori, Shunsuke ; Oe, Masashi ; Kometani, Mitsuhiro ; Sawamura, Toshitaka ; Cheng, Yuan ; Maeda, Yuji ; Namiki, Mikio ; Ino, Hidekazu ; Fujino, Noboru ; Uchiyama, Katsuharu ; Tsubokawa, Toshinari ; Yamagishi, Masakazu ; Nakamura, Yasuhiro ; Ono, Katsuhiko ; Sasano, Hironobu ; Demura, Yoshiki ; Takeda, Yoshiyu
概要:
金沢大学医薬保健研究域医学系<br />Objective: Nuclear receptors are involved in a wide variety of functions, including aldosteronogenes
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is. Nuclear receptor families NR4A [nerve growth factor-induced clone B (NGFIB), Nur-related factor 1 (NURR1) and neuron-derived orphan receptor 1 (NOR1)] and NR2F [chicken ovalbumin upstream promoter-transcription factor 1 (COUP-TFI), COUP-TFII and NR2F6) activate, whereas NR5A1 [steroidogenic factor 1 (SF1)] represses CYP11B2 (aldosterone synthase) gene transcription. The present study was undertaken to elucidate the mechanism of differential regulation of nuclear receptors between cardiovascular and adrenal tissues. Methods: We collected tissues of artery (n = 9), cardiomyopathy muscle (n = 9), heart muscle (noncardiomyopathy) (n = 6), adrenal gland (n = 9) and aldosterone-producing adenoma (APA) (n = 9). 5′-rapid amplification of cDNA ends (RACE) identified transcription start sites. Multiplex reverse-transcription PCR (RT-PCR) determined use of alternative noncoding exons 1 (ANEs). Results: In adrenocortical H295R cells, angiotensin II, KCl or cAMP, all stimulated CYP11B2 transcription and NR4A was upregulated, whereas NR2F and NR5A1 were downregulated. 5′-RACE and RT-PCR revealed four ANEs of NGFIB (NR4A1), three of NURR1 (NR4A2), two of NOR1 (NR4A3) and two of SF1 (NR5A1) in cardiovascular and adrenal tissues. Quantitative multiplex RT-PCR showed NR4A and NR5A1 differentially employed multiple ANEs in a tissue-specific manner. The use of ANEs of NGFIB and NURR1 was significantly different between APA and artery. Changes in use of ANEs of NGFIB and NOR1 were observed between cardiomyopathy and noncardiomyopathy. The NR4A mRNA levels in artery were high compared with cardiac and adrenal tissues, whereas the NR5A1 mRNA level in adrenal tissues was extremely high compared with cardiovascular tissues. Conclusion: NR4A and NR5A1 genes are complex in terms of alternative promoter use. The use of ANEs may be associated with the pathophysiology of the heart and adrenal gland. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.
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| 2.
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論文
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Karashima, Shigehiro ; Yoneda, Takashi ; Kometani, Mitsuhiro ; Ohe, Masashi ; Mori, Shunsuke ; Sawamura, Toshitaka ; Furukawa, Kenji ; Seta, Takashi ; Yamagishi, Masakazu ; Takeda, Yoshiyu
概要:
The mineralocorticoid receptor (MR) is expressed in the kidneys and in adipose tissue, and primary aldosteronism (PA) is
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associated with metabolic syndrome. This study assessed the effects of MR blockade by eplerenone (EPL) and spironolactone (SPL) on blood pressure (BP) and metabolic factors in patients with PA. Fifty-four patients with PA were treated with one of two MRAs, EPL (25-100 mg daily, n=27) or SPL (12.5-100 mg daily, n=27) for 12 months. Visceral (VAT) and subcutaneous adipose tissue were quantified using CT and FatScan imaging analysis software. Body mass index, homeostasis model assessment-insulin resistance (HOMA-IR), serum creatinine, potassium and lipids, urinary albumin excretion (UAE) and plasma aldosterone concentration (PAC) and plasma renin activity (PRA) were measured before and after treatment. EPL and SPL decreased BP and increased serum potassium levels to similar degrees. PAC and PRA did not differ between the two groups. Although treatment with the MRAs did not change HOMA-IR or serum lipids, they significantly decreased UAE and VAT (P<0.05). These results suggest that EPL and SPL are effective and safe for the treatment of PA. The long-term metabolic and renal effects of these MRAs should be further investigated. © 2016 The Japanese Society of Hypertension. All rights reserved.<br />Embargo Period 6 months
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| 3.
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論文
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Kometani, Mitsuhiro ; Yoneda, Takashi ; Demura, Masashi ; Karashima, Shigehiro ; Mori, Shunsuke ; Oe, Masashi ; Sawamura, Toshitaka ; Okuda, Rika ; Yamagishi, Masakazu ; Takeda, Yoshiyu
概要:
Primary aldosteronism (PA) is a major cause of secondary hypertension, divided into two subtypes: unilateral and bilater
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al. Unilateral PA (u-PA) is surgically-curable. Medical treatment with mineralocorticoid receptors antagonists is recommended as a second-line treatment when the patients are not candidate for surgical treatment. The present case was a 39-year-old woman with u-PA, who had refused surgery, had suffered from adverse effects of medical treatment. She was treated with transcatheter adrenal arterial embolization (TAAE). Her blood pressure had been well controlled without progression of cardiorenovascular damage for 12 years. TAAE can be the third treatment option for u-PA patients. © 2016 The Japanese Society of Internal Medicine.
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