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Featured researches published by Ryotaro Wake.


Hypertension Research | 2005

Excess aldosterone under normal salt diet induces cardiac hypertrophy and infiltration via oxidative stress.

Kaoru Yoshida; Shokei Kim-Mitsuyama; Ryotaro Wake; Yasuhiro Izumiya; Yasukatsu Izumi; Tokihito Yukimura; Makiko Ueda; Minoru Yoshiyama; Hiroshi Iwao

Aldosterone is known to play a role in the pathophysiology of some cardiovascular diseases. However, previous studies on aldosterone infusion have been mostly performed in animals receiving sodium loading and uninephrectomy, and thus the cardiac action of aldosterone alone remains to be fully clarified. The present study was undertaken to investigate the direct cardiac action of aldosterone infusion alone in rats not subjected to salt loading and uninephrectomy. Aldosterone (0.75 μg/h) was subcutaneously infused into rats via an osmotic minipump for 14 days. Aldosterone infusion, under a normal salt diet, induced only a slight increase in the blood pressure of normal rats throughout the infusion. However, aldosterone significantly induced cardiac hypertrophy, as shown by echocardiography and measurement of cardiomyocyte cross-sectional area. Furthermore, aldosterone caused not only cardiac interstitial macrophage infiltration but also cardiac focal inflammatory lesions, which were associated with an increase in cardiac monocyte chemoattractant protein-1 (MCP-1) and osteopontin mRNA. The slight elevation of blood pressure by aldosterone infusion was completely prevented by tempol, the superoxide dismutase mimetic. However, tempol failed to suppress cardiac hypertrophy, the formation of inflammatory lesions, and upregulation of cardiac MCP-1 and osteopontin by aldosterone, while N-acetylcysteine could inhibit all of them. Our data provide evidence that aldosterone alone can induce cardiac hypertrophy and severe inflammatory response in the heart, independently of blood pressure, even in the absence of salt loading or nephrectomy. Aldosterone seems to induce cardiac inflammation and gene expression via oxidative stress that is inhibited by N-acetylcysteine but not by tempol.


Recent Patents on Cardiovascular Drug Discovery | 2009

Gender differences in ischemic heart disease.

Ryotaro Wake; Minoru Yoshiyama

Coronary artery disease (CAD) is a leading cause of mortality and morbidity in most developed countries. Gender-related differences have been found in the presentation, prevalence, and clinical outcomes of CAD in many studies. Compared to women, men present with ST-segment elevation myocardial infarction more often and have a higher prevalence of CAD. These findings indicate that gender may have an important influence on CAD. Appropriate diagnosis, prevention, recent patent inventions, and treatment will improve the care of all patients. It is therefore necessary to consider the differences in the features of ischemic heart disease between men and women when examining patients. Novel drugs for tailor-made therapy based on gender differences should be developed for the treatment of CAD in future.


Gene Therapy | 2006

Dominant-negative c-Jun inhibits rat cardiac hypertrophy induced by angiotensin II and hypertension

Shokei Kim-Mitsuyama; Yasukatsu Izumi; Yasuhiro Izumiya; M Namba; Kaoru Yoshida; Ryotaro Wake; Minoru Yoshiyama; Hiroshi Iwao

Cardiac activator protein-1 (AP-1), composed of c-Jun, is significantly activated by hypertension or angiotensin II (AngII). This study was undertaken to elucidate whether c-Jun could be the potential target for treatment of cardiac hypertrophy. We constructed recombinant adenovirus carrying dominant-negative mutant of c-Jun (Ad.DN-c-Jun). Using catheter-based technique of adenoviral gene transfer, we achieved global myocardial transduction of DN-c-Jun in rats, to specifically inhibit cardiac AP-1. (1) AngII (200 ng/kg/min) infusion in rats caused cardiac hypertrophy, increased cardiac p70S6 kinase activity by 1.3-fold (P<0.05) and enhanced the gene expression of cardiac hypertrophic markers. Ad.DN-c-Jun, which was transferred to the heart 2 days before AngII infusion, prevented cardiac hypertrophy (P<0.01), decreased p70S6 kinase phosphorylation (P<0.05), and suppressed cardiac gene expression of brain natriuretic peptide, collagen I, III, and IV, monocyte chemoattractant protein-1 (MCP-1) and plasminogen activator inhibitor-1 (PAI-1) (P<0.01). (2) In genetically hypertensive rats with cardiac hypertrophy, cardiac gene transfer of Ad.DN-c-Jun, without affecting hypertension, regressed cardiac hypertrophy (P<0.05), and suppressed p70S6 kinase phosphorylation by 20% (P<0.05) and suppressed the enhanced expression of collagen I, III, and IV, MCP-1 and PAI-1. These results provided the first evidence that in vivo blockade of cardiac c-Jun inhibits pathologic cardiac hypertrophy.


Environmental health insights | 2008

The Gravitation of the Moon Plays Pivotal Roles in the Occurrence of the Acute Myocardial Infarction

Ryotaro Wake; Junichi Yoshikawa; Kazuo Haze; Shinichiro Otani; Takayoshi Yoshimura; Iku Toda; Masaki Nishimoto; Takahiko Kawarabayashi; Atsushi Tanaka; Kenei Shimada; Hidetaka Iida; Kazuhide Takeuchi; Minoru Yoshiyama

Acute myocardial infarction (AMI) is a social burden. However, being able to predict AMI could lead to prevention. A previous study showed only the relation between the lunar phase and the occurrence of AMI, but the period it takes for the moon to orbit around the earth and the period of the lunar phase differ. This study investigated the effect of the gravitation of the moon on AMI. Data was comprised of 1369 consecutive patients with first AMI at 5 hospitals from October, 1984 to December, 1997. The universal gravitation of the moon was calculated and compared to the earth onset time of AMI. Universal gravitation of the moon was derived by G*m/d2 (G: universal gravitation constant, m: the mass of the moon, d: the distance between the center of the moon and the center of the earth). The relationship between m/d2 and the cases of AMI was determined. There was an increase in cases, when there is a distance of more than 399864 km from the center of the earth to the center of the moon. The gravitation of more than 399864 km was determined to be weaker gravitation. It is confirmed that the number of AMI patients significantly increases at weaker gravitation periods in this multicenter trial. In conclusion, these results suggest that the gravitation of the moon may have an influence on the occurrence of AMI.


Journal of the American College of Cardiology | 2010

Ruptured Aneurysm of the Sinus of Valsalva Demonstrated by 3-Dimensional Echocardiography

Takanori Kusuyama; Hidetaka Iida; Hiroaki Takeshita; Ryotaro Wake; Shinichi Shimodozono; Yukio Yamada

![Figure][1] [![Graphic][3] ][3][![Graphic][4] ][4][![Graphic][5] ][5][![Graphic][6] ][6] A 67-year-old Japanese woman was admitted to our hospital because of orthopnea. Transthoracic echocardiography (Vivid7, GE Healthcare, Milwaukee, Wisconsin) demonstrated a ruptured


Environmental health insights | 2010

The Effect of the Gravitation of the Moon on Frequency of Births

Ryotaro Wake; Takuya Misugi; Kenei Shimada; Minoru Yoshiyama

The purpose of this study was to examine the influence of the gravitation of the Moon on the frequency of births in Kyoto, Japan. A retrospective cohort analysis of 1007 consecutive births without the use of the induction agents was conducted on a population of births in a private midwife hospital from January, 1966 to December, 2000. There was a significant increase in the cases of births, when the gravitation of the Moon to the Earth was less than 31.5 N. Results of this study suggest that the gravitation of the Moon has an influence on the frequency of births.


Archive | 2012

Gender Differences in Coronary Artery Disease

Ryotaro Wake; Minoru Yoshiyama

Coronary artery disease (CAD) is a leading cause of mortality and morbidity in most developed countries [1]. Many studies have found gender-related differences in the presentations, prevalence, and clinical outcomes of CAD [2-4]. CAD first presents itself in women approximately 10 years later than in men, most commonly after menopause [5]. The worldwide INTERHEART study, a large study of more than 52000 individuals with MI, first demonstrated that this approximate 8 to 10 year difference in age at onset holds widely around the world, across various socioeconomic, climatic, and cultural environments. Although coronary artery disease in general is manifestated earlier in less developed countries, the age gap in time of onset between men and women is universal (Table 1) [6].


Hypertension Research | 2016

Erratum: Excess aldosterone under normal salt diet induces cardiac hypertrophy and infiltration via oxidative stress (Hypertension Research (2016) 39, (482)) doi: 10.1038/hr.2016.33

Kaoru Yoshida; Shokei Kim-Mitsuyama; Ryotaro Wake; Yasuhiro Izumiya; Yasukatsu Izumi; Tokihito Yukimura; Makiko Ueda; Minoru Yoshiyama; Hiroshi Iwao

Correction to: Hypertension Research (2005) 28, 447–455; doi:10.1291/hypres.28.447 It has come to the authors’ attention that three representative images used in Figure 2(B) of this article were incorrect. The figure with correct representative images is presented below. This correction does not affect the results or the conclusions of this manuscript.


Hypertension Research | 2016

Corrigendum: Excess aldosterone under normal salt diet induces cardiac hypertrophy and infiltration via oxidative stress

Kaoru Yoshida; Shokei Kim-Mitsuyama; Ryotaro Wake; Yasuhiro Izumiya; Yasukatsu Izumi; Tokihito Yukimura; Makiko Ueda; Minoru Yoshiyama; Hiroshi Iwao

Correction to: Hypertension Research (2005) 28, 447–455; doi:10.1291/hypres.28.447 It has come to the authors’ attention that three representative images used in Figure 2(B) of this article were incorrect. The figure with correct representative images is presented below. This correction does not affect the results or the conclusions of this manuscript.


Archive | 2013

Echocardiographic Evaluation of Left Ventricular Diastolic Function

Ryotaro Wake; Shota Fukuda; Hiroki Oe; Yukio Abe; JunichiYoshikawa; Minoru Yoshiyama

Approximately half of patients with a diagnosis of heart failure have a normal left ventricular (LV) ejection fraction (EF) without valve disease which is defined as diastolic heart failure (DHF), because it is attributed to LV diastolic dysfunction.[2] Studies examining prevalence of diastolic heart failure in hospitalized patients or in patients undergoing outpatient diag‐ nostic screening and prospective community based studies have shown that the prevalence of diastolic heart failure approaches 50%.[3-5]

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Hidetaka Iida

Memorial Hospital of South Bend

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