基本情報
研究キーワード
4研究分野
1委員歴
5-
2012年 - 2014年
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2014年
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2014年
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2014年
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2012年
受賞
7-
2010年3月
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2009年5月
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2006年11月
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2002年7月
論文
969-
Journal of the American Heart Association 14(2) e034627 2025年1月21日BACKGROUND: The effect of worsening renal function and baseline chronic kidney disease (CKD) on outcomes in patients with chronic coronary syndrome in the setting of optimal medical therapy remains unknown. METHODS AND RESULTS: The REAL-CAD (Randomized Evaluation of Aggressive or Moderate Lipid Lowering Therapy With Pitavastatin in Coronary Artery Disease) study is a prospective, multicenter, randomized trial of high-dose (pitavastatin 4 mg/day) or low-dose (pitavastatin 1 mg/day) statin therapy in 12 118 patients with chronic coronary syndrome. The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, stroke, or unstable angina requiring hospitalization (major adverse cardiac and cerebral events [MACCE]). CKD was defined as an estimated glomerular filtration rate [eGFR] <60 mL/min per 1.73 m2. WRF was defined as a decrease in eGFR ≥20% in the initial year; borderline renal function was an annual decrease of 0%<eGFR<20%, and stable renal function was no decrease. Of 12 118 patients, 4340 had baseline CKD and 7778 did not. The rate of MACCE at 5 years was significantly lower in those without (5.5%) versus with CKD (9.5%) (P<0.0001). After excluding 1247 patients who had MACCE, were censored, or missing eGFR within 1 year, 10 871 patients were included. Of these, 3885 were baseline CKD and the remaining 6986 did not have baseline CKD. Of the 10 871 patients, 577 patients had WRF, 6014 patients showed borderline renal function, and the remaining 4280 patients maintained stable renal function. In patients with CKD, WRF was an independent predictor for MACCE at 4 years as compared with stable renal function (hazard ratio [HR]: 1.67; [95% CI, 1.03-2.73; P=0.039]). In patients without CKD, borderline renal function was a significant predictor for MACCE at 4 years compared with stable renal function (HR: 1.40 [95% CI, 1.03-1.91; P=0.032]). CONCLUSIONS: Baseline CKD was an independent predictor for MACCE in patients with CCS. WRF was a significant predictor for MACCE in patients with CKD. Because borderline renal function was an independent predictor for MACCE even in patients without CKD, mild-to-moderate annual declines of eGFR should be carefully monitored (NCT01042730). REGISTRATION: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT01042730.
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International Journal of Molecular Sciences 26(2) 556-556 2025年1月10日 査読有り
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IJC Heart & Vasculature 54 101507-101507 2024年10月
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Hypertension research : official journal of the Japanese Society of Hypertension 2024年9月19日The Japanese Society of Hypertension have established a blood pressure (BP) target of 130/80 mmHg for patients with coronary artery disease (CAD). We evaluated the data of 8793 CAD patients in the Clinical Deep Data Accumulation System database who underwent cardiac catheterization at six university hospitals and the National Cerebral and Cardiovascular Center (average age 70 ± 11 years, 78% male, 43% with acute coronary syndrome [ACS]). Patients were divided into two groups based on whether or not they achieved the guideline-recommended BP of <130/80 mmHg. We analyzed the relationship between BP classification and major adverse cardiac and cerebral event (MACCE) separately in two groups: those with ACS and those with chronic coronary syndrome (CCS). During an average follow-up period of 33 months, 710 MACCEs occurred. A BP below 130/80 mmHg was associated with fewer MACCEs in both the overall (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.70-1.00, p = 0.048) and the ACS group (HR 0.67, 95%CI 0.51-0.88, p = 0.003). In particular, stroke events were also lower among those with a BP below 130/80 mmHg in both the overall (HR 0.69, 95%CI 0.53-0.90, p = 0.006) and ACS groups (HR 0.44, 95%CI 0.30-0.67, p < 0.001). In conclusion, the achievement of BP guidelines was associated with improved outcomes in CAD patients, particularly in reducing stroke risk among those with ACS.
MISC
1923-
Circulation journal : official journal of the Japanese Circulation Society 69 43-43 2005年3月1日
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Circulation journal : official journal of the Japanese Circulation Society 69 648-648 2005年3月1日
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Circulation journal : official journal of the Japanese Circulation Society 69 115-115 2005年3月1日
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Circulation journal : official journal of the Japanese Circulation Society 69 112-112 2005年3月1日
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Circulation journal : official journal of the Japanese Circulation Society 69 115-115 2005年3月1日
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Circulation journal : official journal of the Japanese Circulation Society 69 248-248 2005年3月1日
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Circulation journal : official journal of the Japanese Circulation Society 69 233-233 2005年3月1日
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Circulation journal : official journal of the Japanese Circulation Society 69 233-233 2005年3月1日
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Circulation journal : official journal of the Japanese Circulation Society 69 253-253 2005年3月1日
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Circulation journal : official journal of the Japanese Circulation Society 69 393-393 2005年3月1日
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Circulation journal : official journal of the Japanese Circulation Society 69 397-397 2005年3月1日
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Circulation journal : official journal of the Japanese Circulation Society 69 392-392 2005年3月1日
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Circulation journal : official journal of the Japanese Circulation Society 69 397-397 2005年3月1日
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Circulation journal : official journal of the Japanese Circulation Society 69 382-382 2005年3月1日
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Circulation journal : official journal of the Japanese Circulation Society 69 155-155 2005年3月1日
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Circulation journal : official journal of the Japanese Circulation Society 69 176-176 2005年3月1日
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Circulation journal : official journal of the Japanese Circulation Society 69 175-176 2005年3月1日
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Circulation journal : official journal of the Japanese Circulation Society 69 155-155 2005年3月1日
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Circulation journal : official journal of the Japanese Circulation Society 69 175-175 2005年3月1日
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Internal medicine (Tokyo, Japan) 44(3) 256-60 2005年3月 査読有り
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International heart journal 46(2) 265-77 2005年3月 査読有り
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Arteriosclerosis, thrombosis, and vascular biology 25(2) 341-7 2005年2月 査読有りOBJECTIVE: Transforming growth factor-beta1 (TGF-beta1) controls the expression of numerous genes, including smooth muscle cell (SMC)-specific genes and extracellular matrix protein genes. Here we investigated whether c-Src plays a role in TGF-beta1 signaling in mouse embryonic fibroblast C3H10T1/2 cells. METHODS AND RESULTS: TGF-beta1 induction of the SMC contractile protein SM22alpha gene expression was inhibited by PP1 (an inhibitor of Src family kinases) or by C-terminal Src kinase (a negative regulator of c-Src). Induction of SM22alpha by TGF-beta1 was markedly attenuated in SYF cells (c-Src(-), Yes(-), and Fyn(-)) compared with Src(++) cells (c-Src(++), Yes(-), and Fyn(-)). PP1 also inhibited the TGF-beta1-induced expression of serum response factor (SRF), a transcription factor regulating the SMC marker gene expression. Confocal immunofluorescence analysis showed that TGF-beta1 stimulates production of hydrogen peroxide. Antioxidants such as catalase or NAD(P)H oxidase inhibitors such as apocynin inhibited the TGF-beta1-induced expression of SM22alpha. Furthermore, we demonstrate that TGF-beta1 induction of the plasminogen activator inhibitor-1 (PAI-1) gene, which is known to be dependent on Smad but not on SRF, is inhibited by PP1 and apocynin. CONCLUSIONS: Our results suggest that TGF-beta1 activates c-Src and generates hydrogen peroxide through NAD(P)H oxidase, and these signaling pathways lead to the activation of specific sets of genes, including SM22alpha and PAI-1. TGF-beta1 controls the expression of numerous genes, including SM22alpha and PAI-1. We investigated whether c-Src plays a role in TGF-beta1 signaling. TGF-beta1 induction of such genes was significantly reduced in Src family tyrosine kinase-deficient cells, and Csk and pharmacological inhibitors for Src family kinases or antioxidants inhibit the effects of TGF-beta1. These results indicate that c-Src and hydrogen peroxide are required for TGF-beta1 signaling.
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Nippon rinsho. Japanese journal of clinical medicine 63(7) 1273-1283 2005年
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International Journal of KAATSU Training Research 1(2) 57-64 2005年KAATSU training is a novel method for strength training to induce muscle strength and hypertrophy. The purpose of the present study was to investigate the hemodynamic and autonomic nervous responses to the restriction of femoral blood flow by KAATSU. Ultrasonography, echocardiography and impedance cardiography were performed in ten healthy male volunteers aged 34 ± 1.5 before (pre), during and after (post) pressurization on both legs with KAATSU belts placed around proximal portion of both legs. The parameters measured were as follows; the superficial femoral arterial blood flow, left ventricular end-diastolic/systolic dimension (LVDd/LVDs), cardiac output (CO), stroke volume (SV), diameter of inferior vena cava (IVC), heart rate (HR), mean blood pressure (mBP), total peripheral resistance (TPR) and heart rate variability (HRV). The pressurization on both legs with KAATSU suppressed venous blood flow, and markedly induced pooling of blood into the legs with pressure-dependent reduction of femoral arterial blood flow. The application of 200 mmHg KAATSU decreased femoral arterial blood flow, LVDd, CO, SV and IVC significantly. HR tended to increase, and TPR increased significantly, but mBP did not change significantly. In addition, high frequency (HFRR), a marker of parasympathetic activity, decreased during KAATSU, while LFRR/HFRR, a quantitative marker of sympathetic autonomic nervous activity, increased significantly. These results indicate that the application of KAATSU on both legs induces venous pooling in the legs, and then inhibits venous return. The reduction of venous return causes a decrease of IVC diameter, cardiac size and stroke volume with an increase in TPR and LFRR/HFRR. Thus, the KAATSU training appears to become a useful method for potential countermeasure like lower body negative pressure (LBNP) against orthostatic intolerance for long-term bed rest or space flight as well as strength training to induce muscle strength and hypertrophy.
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FREE RADICAL BIOLOGY AND MEDICINE 39 S154-S155 2005年
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日本生理学会大会発表要旨集 2005 S25-S25 2005年Cardiovascular function and frequencies of onset of cardiovascular diseases show circadian oscillation. Furthermore, cultured vascular endothelial cells and cardiomyocytes showed circadian oscillation of clock genes expression, suggesting the existence of the peripheral clock in cardiovascular systems. To elucidate the functional relevance of the peripheral clock in cardiovascular system, we first tried to identify the target genes of the peripheral clock. We demonstrated that PAI-1 mRNA levels exhibited circadian variation and that CLOCK and BMAL increased PAI-1gene expression mediated through the E-box sites. The circadian oscillation of PAI-1 gene expression is responsible for the decreased fibrinolytic activity that attributes to the morning onset of myocardial infarction. We further identified several target genes of the peripheral clock by cDNA microarray analysis using RNA from vascular endothelial cells. We are analyzing the function of these genes in cardiovascular system. We next generated transgenic mice in which Cry1, a negative regulator of the molecular clock, is overexpressed specifically in vascular endothelial cells to analyze the function of the peripheral clock separately from the central clock. Taken together, these results suggest that cardiovascular systems have their own peripheral clocks and at least in part, they may regulate the circadian oscillation of cardiovascular function directly. These results potentially provide a molecular basis for the circadian variation of cardiovascular function and novel strategies for the treatment of cardiovascular diseases. <b>[Jpn J Physiol 55 Suppl:S25 (2005)]</b>
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ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY 24(11) E185-E187 2004年11月
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NEW ENGLAND JOURNAL OF MEDICINE 351(19) 2017-2018 2004年11月
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Circulation journal : official journal of the Japanese Circulation Society 68 897-897 2004年10月20日
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Circulation journal : official journal of the Japanese Circulation Society 68 889-889 2004年10月20日
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Cloning of adiponectin receptors that mediate antidiabetic metabolic effects (vol 423, pg 762, 2003)NATURE 431(7012) 1123-1123 2004年10月
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CIRCULATION 110(17) 218-218 2004年10月
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CIRCULATION 110(17) 154-154 2004年10月
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CIRCULATION 110(17) 146-146 2004年10月
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CIRCULATION 110(17) 288-288 2004年10月
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CIRCULATION 110(17) 786-786 2004年10月
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CIRCULATION 110(17) 176-176 2004年10月
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Heart (British Cardiac Society) 90(10) 1211-3 2004年10月 査読有り
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Arteriosclerosis, thrombosis, and vascular biology 24(9) 1602-7 2004年9月 査読有り
書籍等出版物
21-
Springer 2009年 (ISBN: 9784431877745)
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Signal Transduction and Cardiac Hypertrophy (Naranjan S. Dhalla, Larry Hryshko, Elissavet Kardami, Pawan K. Singal, KLUWER ACADEMIC PUBLISHERS) 2003年
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Signal Transduction and Cardiac Hypertrophy (Naranjan S. Dhalla, Larry Hryshko, Elissavet Kardami, Pawan K. Singal, KLUWER ACADEMIC PUBLISHERS) 2003年
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Rapid Cycle Real-Time PCR : methods and applications 2001年
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in"The Hypertrophied Heart" 2000年
共同研究・競争的資金等の研究課題
91-
日本学術振興会 科学研究費助成事業 2023年4月 - 2026年3月
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日本学術振興会 科学研究費助成事業 2020年7月 - 2023年3月
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日本学術振興会 科学研究費助成事業 2019年4月 - 2023年3月
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日本学術振興会 科学研究費助成事業 2019年4月 - 2023年3月
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日本学術振興会 科学研究費助成事業 2018年6月 - 2023年3月