著者
Miki Nonaka Nagomi Kurebayashi Takashi Murayama Masami Sugihara Kiyoshi Terawaki Seiji Shiraishi Kanako Miyano Hiroshi Hosoda Shosei Kishida Kenji Kangawa Takashi Sakurai Yasuhito Uezono
出版者
The Japan Endocrine Society
雑誌
Endocrine Journal (ISSN:09188959)
巻号頁・発行日
vol.64, no.Suppl., pp.S35-S39, 2017 (Released:2017-06-24)
参考文献数
14
被引用文献数
2 9

Cancer was considered an incurable disease for many years; however, with the development of anticancer drugs and state-of-the art technologies, it has become curable. Cardiovascular diseases in patients with cancer or induced by cancer chemotherapy have recently become a great concern. Certain anticancer drugs and molecular targeted therapies cause cardiotoxicity, which limit the widespread implementation of cancer treatment and decrease the quality of life in cancer patients significantly. The anthracycline doxorubicin (DOX) causes cardiotoxicity. The cellular mechanism underlying DOX-induced cardiotoxicity include free-radical damage to cardiac myocytes, leading to mitochondrial injury and subsequent death of myocytes. Recently, circulating orexigenic hormones, ghrelin and des-acyl ghrelin, have been reported to inhibit DOX-induced cardiotoxicity. However, little is known about the molecular mechanisms underlying their preventive effects. In the present study, we show the possible mechanisms underlying the effects of ghrelin and des-acyl ghrelin against DOX-induced cardiotoxicity through in vitro and in vivo researches.
著者
Takeshi TOKUDOME Kenji KANGAWA
出版者
The Japan Academy
雑誌
Proceedings of the Japan Academy, Series B (ISSN:03862208)
巻号頁・発行日
vol.95, no.8, pp.459-467, 2019-10-11 (Released:2019-10-11)
参考文献数
38
被引用文献数
15

Ghrelin, a growth hormone-releasing peptide first discovered in rat stomach in 1999, is a ligand for the growth hormone secretagogue receptor. It participates in the regulation of diverse processes, including energy balance and body weight maintenance, and appears to be beneficial for the treatment of cardiovascular diseases. In animal models of chronic heart failure, ghrelin improves cardiac function and remodeling; these findings have been recapitulated in human patients. In other animal models, ghrelin effectively diminishes pulmonary hypertension. Moreover, ghrelin administration early after myocardial infarction decreased the frequency of fatal arrhythmia and improved survival rate. In ghrelin-deficient mice, endogenous ghrelin protects against fatal arrhythmia and promotes remodeling after myocardial infarction. Although the mechanisms underlying the effects of ghrelin on the cardiovascular system have not been fully elucidated, its beneficial effects appear to be mediated through regulation of the autonomic nervous system. Ghrelin is a promising therapeutic agent for cardiac diseases.
著者
Takeshi Yagyu Satoshi Yasuda Noritoshi Nagaya Kaori Doi Takeshi Nakatani Kazuhiro Satomi Wataru Shimizu Kengo Kusano Toshihisa Anzai Teruo Noguchi Hajime Ohgushi Soichiro Kitamura Kenji Kangawa Hisao Ogawa
出版者
The Japanese Circulation Society
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
pp.CJ-18-1179, (Released:2019-05-17)
参考文献数
45
被引用文献数
11

Background:Mesenchymal stem cells (MSCs), which have the potential to differentiate into cardiomyocytes or vascular endothelial cells, have been used clinically as therapy for cardiomyopathy. In this study, we aimed to evaluate the long-term follow-up results.Methods and Results:We studied 8 patients with symptomatic heart failure (HF) on guideline-directed therapy (ischemic cardiomyopathy, n=3; nonischemic cardiomyopathy, n=5) who underwent intracardiac MSC transplantation using a catheter-based injection method between May 2004 and April 2006. Major adverse events and hospitalizations were investigated up to 10 years afterward. Compared with baseline, there were no significant differences in B-type natriuretic peptide (BNP) (from 211 to 173 pg/mL), left ventricular ejection fraction (LVEF) (from 24% to 26%), and peak oxygen uptake (from 16.5 to 19.2 mL/min/kg) at 2 months. During the follow-up period, no patients experienced serious adverse events such as arrhythmias. Three patients died of pneumonia in the 1st year, liver cancer in the 6th year, and HF in the 7th year. Of the remaining 5 patients, 3 patients were hospitalized for exacerbated HF, 1 of whom required heart transplantation in the 2nd year; 2 patients survived for 10 years without worsening HF.Conclusions:The results of this exploratory study of intracardiac MSCs administration suggest further research regarding the feasibility and efficacy is warranted.
著者
Hiroyuki Ariyasu Hiroshi Iwakura Naoichiro Yukawa Toshinori Murayama Masayuki Yokode Harue Tada Kenichi Yoshimura Satoshi Teramukai Tatsuya Ito Akira Shimizu Atsushi Yonezawa Kenji Kangawa Tsuneyo Mimori Takashi Akamizu
出版者
(社)日本内分泌学会
雑誌
Endocrine Journal (ISSN:09188959)
巻号頁・発行日
pp.EJ14-0088, (Released:2014-04-17)
被引用文献数
6 20

The majority of patients with systemic sclerosis (SSc) have gastrointestinal (GI) tract involvement, but therapies using prokinetic agents are usually unsatisfactory. Ghrelin stimulates gastric motility in healthy human volunteers. In this study, we investigated whether ghrelin could improve gastric emptying in patients with gastrointestinal symptoms due to SSc. The study was performed in a randomized, double-blind, placebo-controlled crossover fashion on two occasions. Ten SSc patients with GI tract involvement received an infusion of either ghrelin (5.0 μg/kg) or saline, and gastric emptying rate was evaluated by 13C-acetic acid breath test. Gastric emptying was significantly accelerated by ghrelin infusion in patients with SSc (ghrelin vs. saline: 43.3 ± 11.4 min vs. 53.4 ± 5.4 min, P≡0.03). No serious adverse effects were observed. Our results suggest that ghrelin might represent a new therapeutic approach for GI tract involvement in patients with SSc.