- 著者
- 中川 靖章 錦見 俊雄 桑原 宏一郎 岡 昌吾 木下 秀之 中尾 一泰 趙 晃済 稲住 英明 加藤 貴雄 中尾 一和 木村 剛 Nishida Motohiro Kato Takao Fukushima Hiroyuki Yamashita Jun K. Wijnen Wino J. Creemers Esther E. Kangawa Kenji Minamino Naoto Nakao Kazuwa Kimura Takeshi
- 出版者
- Wiley Blackwell
- 雑誌
- Journal of the American Heart Association (ISSN:20479980)
- 巻号頁・発行日
- vol.6, no.2, 2017-02
Background-Recent studies have shown that plasma levels of the biologically inactive prohormone for brain natriuretic peptide (proBNP) are increased in patients with heart failure. This can contribute to a reduction in the effectiveness of circulating BNP and exacerbate heart failure progression. The precise mechanisms governing the increase in proBNP remain unclear, however. Methods and Results-We used our recently developed, highly sensitive human proBNP assay system to investigate the mechanisms underlying the increase in plasma proBNP levels. We divided 53 consecutive patients hospitalized with heart failure into 2 groups based on their aortic plasma levels of immunoreactive BNP. Patients with higher levels exhibited more severe heart failure, a higher proportion of proBNP among the immunoreactive BNP forms secreted from failing hearts, and a weaker effect of BNP as estimated from the ratio of plasma cyclic guanosine monophosphate levels to log-transformed plasma BNP levels. Glycosylation at threonines 48 and 71 of human proBNP contributed to the increased secretion of proBNP by attenuating its processing, and GalNAc-transferase (GALNT) 1 and 2 mediated the glycosylation-regulated increase in cardiac human proBNP secretion. Cardiac GALNT1 and 2 expression was suppressed by microRNA (miR)-30, which is abundantly expressed in the myocardium of healthy hearts, but is suppressed in failing hearts. Conclusions-We have elucidated a novel miR-30-GALNT1/2 axis whose dysregulation increases the proportion of inactive proBNP secreted by the heart and impairs the compensatory actions of BNP during the progression of heart failure.
- 著者
- Yamashita Takeshi Ogawa Satoshi Aizawa Yoshifusa Atarashi Hirotsugu Inoue Hiroshi Ohe Tohru Okumura Ken Kato Takao Kamakura Shiro Kumagai Koichiro Kurachi Yoshihisa Kodama Itsuo Koretsune Yukihiro Saikawa Tetsunori Sakurai Masayuki Sugi Kaoru Nakaya Haruaki Nakayama Toshio Hirai Makoto Fukatani Masahiko Mitamura Hideo Yamazaki Tsutomu
- 出版者
- 社団法人日本循環器学会
- 雑誌
- Circulation journal : official journal of the Japanese Circulation Society (ISSN:13469843)
- 巻号頁・発行日
- vol.67, no.9, pp.738-741, 2003-08-20
- 被引用文献数
- 22 50
The Japanese Rhythm Management Trial for Atrial Fibrillation (J-RHYTHM study) is a randomized comparative evaluation of rate control and rhythm control, both combined with antithrombotic therapy, as therapeutic strategies for the treatment of atrial fibrillation (AF). This study differs from the earlier AFFIRM and RACE studies in that it has a composite primary end-point representing mortality and also physical/psychological disablement (total mortality, symptomatic cerebral infarction, systemic embolism, major bleeding, hospitalization for heart failure requiring intravenous administration of diuretics, and patient disablement). Patients' will to change the therapeutic strategy to the other is also considered as an end-point representing disablement under the assigned strategy. The secondary end-point includes quality of life scores and the efficacy and safety of drugs used in treating AF. The J-RHYTHM study emphasizes patient-reported experience and perception of AF-specific disablement, and the safety of antiarrhythmics available in Japan; it will follow 2,600 patients treated at more than 150 sites in Japan for a 3-year period. (Circ J 2003; 67: 738-741)