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
965-
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
1913-
Circulation journal : official journal of the Japanese Circulation Society 72 2008年10月20日
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JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY 45 S6-S6 2008年10月
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CIRCULATION 118(18) S555-S555 2008年10月
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CIRCULATION 118(18) S557-S557 2008年10月
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HYPERTENSION 52(4) E123-E123 2008年10月
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CIRCULATION 118(18) S431-S431 2008年10月
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CIRCULATION 118(18) S518-S518 2008年10月
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JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY 45 S6-S7 2008年10月
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INTERNATIONAL JOURNAL OF CARDIOLOGY 129(2) 294-296 2008年9月We analyzed 6317 patients with a baseline LDL-cholesterol level of 70 to 130 mg/dL among 13,812 patients of the Japanese Coronary Artery Disease (JCAD) study. We divided the patients into 2 groups according to statin treatment and its lipophilicity. We compared the incidence of all-cause events between 2000 statin-treated patients and 4317 patients without statins during a median follow-up period of 1092 days (range 0 to 1676 days). After propensity score matching (n = 1641, for each group), Kaplan-Meier analysis showed 25% reduction in the incidence of all-cause events with statin treatment (p = 0.0016). The incidence of all-cause events was also compared between 1139 patients with hydrophilic statin and 861 patients with lipophilic statin. After propensity score matching (n= 778, for each group), Kaplan-Meier analysis showed no significant difference in the incidence of all-cause events with respect to lipophilicity. Subgroup analysis of the JCAD study suggested a lipid-independent beneficial treatment effect of statins on all-cause events, and these favorable effects were comparable between the hydrophilic and lipophilic statins. (C) 2007 Elsevier Ireland Ltd. All rights reserved.
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Circulation 118(9) e133-5-E135 2008年8月26日 査読有り
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JOURNAL OF HYPERTENSION 26 S419-S419 2008年6月
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PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY 97(2-3) 282-297 2008年6月Mechano-electrical feedback (MEF) has mainly been studied in isolated single cardiomyocytes using the microelectrode and micropipette techniques, but information regarding its dynamic aspects at the cellular level is limited due to the technical difficulties associated with manipulating single cells and maintaining stable attachment of these devices. To overcome such difficulties, we have combined two experimental methods, namely a carbon fiber technique to hold single myocytes and a ratiometric fluorescence measurement technique to monitor Ca2+ transients or membrane potentials. Following an overview of the experimental technique for stretching myocytes, the results for single rat ventricular myocytes under axial stretching are presented. Ca2+ transients were influenced by the loading conditions and involvement of myofilaments was suspected in regulatory mechanism. Membrane potential measurements during dynamic axial stretching revealed that the action potential duration was prolonged when the stretch was applied during the late phase of twitch contraction, and that depolarization of the resting membrane potential depended on the phase, amplitude and speed of the applied stretch. The amplitude may also modulate the ion selectivity of stretch-activated channels. This combination of the carbon fiber technique with fluorescence measurement could represent a powerful tool for clarifying MEF at the cellular level. (c) 2008 Published by Elsevier Ltd.
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JOURNAL OF HYPERTENSION 26 S78-S78 2008年6月
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JOURNAL OF HYPERTENSION 26 S170-S170 2008年6月
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JOURNAL OF HYPERTENSION 26 S43-S43 2008年6月
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JOURNAL OF HYPERTENSION 26 S513-S513 2008年6月
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Nature clinical practice. Cardiovascular medicine 5(6) 295-295 2008年6月 査読有り
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NATURE CELL BIOLOGY 10(5) 567-574 2008年5月The high mobility group ( HMG) of nuclear proteins regulates expression of many genes through architectural remodelling of the chromatin structure, and formation of multiprotein complexes on promoter/enhancer regions. This leads to the active transcription of their target genes(1-3). Here we show that HMGA2, a member of the HMGA sub-family of HMG proteins, has a critical function in cardiogenesis. Overexpression of HMGA2 enhanced, whereas siRNA-mediated knockdown of HMGA2 blocked, cardiomyocyte differentiation of the embryonal carcinoma cell line P19CL6. Moreover, overexpression of a dominant-negative HMGA2 or morpholino-mediated knockdown of HMGA2 expression blocked normal heart formation in Xenopus laevis embryos, suggesting that HMGA2 has an important role in cardiogenesis both in vitro and in vivo. Mechanistically, HMGA2 associated with Smad1/4 and showed synergistic trans-activation of the gene for a cardiac transcription factor Nkx2.5; a conserved HMGA2 binding site was required for the promoter activity of Nkx2.5 gene, both in P19CL6 cells and in transgenic Xenopus embryos. Thus, HMGA2 is a positive regulator of Nkx2.5 gene expression and is essential for normal cardiac development.
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International heart journal 49(3) 313-27 2008年5月 査読有りA phenotypic change of smooth muscle cells (SMCs) is considered to be critical in the pathogenesis of atherosclerotic lesions such as coronary artery disease (CAD). Mrf-2/ARID5B, a member of the AT-rich interaction domain family of transcription factors, is highly expressed in the cardiovascular system and is believed to play essential roles in the phenotypic change of SMCs through its regulation of SMC differentiation. In addition, recent studies on gene-engineered mice suggested that this transcriptional factor is involved in obesity and adipogenesis, which are critical aspects for the pathogenesis of atherosclerosis. Thus, we hypothesized that genetic variations of the Mrf-2 gene might be associated with susceptibility to CAD. We investigated 11 common genetic variations of Mrf-2 to determine whether they were associated with susceptibility to CAD in 475 CAD subjects and 310 control subjects. The prevalence of homozygotes for the minor allele G of SNP4 (rs2893880) and minor allele G of SNP6 (rs7087507) were significantly more frequent in the control subjects than in patients with CAD (P=0.0002, rs2893880, P=0.0058, rs7087507). Four nearby SNPs (SNP4 to SNP7) (rs2893880, rs10740055, rs7087507 and rs10761600) showed almost complete linkage disequilibrium, and haplotype analysis revealed that the haplotype G (rs2893880)-C (rs10740055)-G (rs7087507)-A (rs10761600) was also significantly negatively associated with susceptibility to CAD (P=0.049). Moreover, these negative disease associations still existed after logistic regression analysis was taken into account to eliminate confounding conventional coronary risk factors. The results implicate possible disease relevance of the polymorphisms in the Mrf-2 gene with susceptibility to CAD. However, a larger scale prospective study is needed to clarify these findings.
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脈管学 : 日本脈管学会機関誌 : the journal of Japanese College of Angiology 48(2) 179-183 2008年4月25日
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Circulation journal : official journal of the Japanese Circulation Society 72 895-895 2008年4月20日
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Circulation journal : official journal of the Japanese Circulation Society 72 2008年4月20日
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Circulation journal : official journal of the Japanese Circulation Society 72(4) 515-20 2008年4月 査読有りBACKGROUND: The benefits of coronary risk modification through medication and other methods have been shown in many clinical studies. Recently, aggressive lowering of low-density lipoprotein-cholesterol (LDL-C) has been shown to confer additive benefits in patients with coronary artery disease (CAD). However, it has not been shown in Japanese patients with CAD if multiple aggressive medical interventions for coronary risk factors are beneficial compared with standard regimens, so a prospective, randomized, open-label, blinded-endpoint (PROBE) multicenter study was designed to evaluate whether aggressive lowering of LDL-C and blood pressure in Japanese hypertensive, hypercholesterolemic CAD patients bestows additional benefits compared with regimens based on current Japanese guidelines. METHODS AND RESULTS: Seventeen hospitals in Japan are participating in the Japanese Coronary Artery Disease II (JCADII) study. Hypertensive and hypercholesterolemic patients who have >or=75% stenosis in at least one major coronary artery according to American Heart Association guidelines will be allocated randomly to receive either conventional or aggressive therapy. Standard therapy for hypertension and hypercholesterolemia aims to reduce blood pressure to <140/90 mmHg and LDL-C concentration to <100 mg/dl. Aggressive therapy aims for targets of <120/80 mmHg and <80 mg/dl, respectively. We plan to recruit 500 patients and follow them up for 3 years. Antihypertensive agents, when used, include the angiotensin receptor blockers candesartan and/or losartan. Antihypercholesterolemic agents, when used, include at least one of the following statins: pravastatin, simvastatin, and atorvastatin. CONCLUSION: The JCADII study will provide important information concerning medical treatment of coronary risk factors in Japanese patients with CAD (UMIN-ID: UMIN000000571).
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Japan Medical Association Journal 51(2) 119-124 2008年3月In order to facilitate safe medical care, it is necessary to understand that there is a multiple hierarchical structure involving various issues ranging from problems of particular individuals to problems affecting the system of medical care as a whole. To prevent medical malpractice, the manager and staff members at the site of work must recognize the probability of errors and control the accuracy of practice, while recognizing that anyone can make a mistake. Although committing an error is not blameworthy in itself, it is necessary to point out deviations from the rules of daily practice and to offer strict guidance to leaders who disregard such deviations or fail to correct them. Organizational reform to concentrate power within the executive body of the hospital is necessary in order to reconcile the operations of individual departments with the overarching policies of the hospital. It is also necessary to systematize the quality of medical care and improve the hospital environment, including medical equipment. In addition, it is important to provide personnel with frequent training and education to increase their skills and knowledge, utilizing pocket manuals, educational DVD materials on medical safety, e-leaming modalities, and mailing lists. The medical field should learn about accuracy and quality control from industry and various other fields.
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Circulation journal : official journal of the Japanese Circulation Society 72 204-204 2008年3月1日
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Circulation journal : official journal of the Japanese Circulation Society 72 168-168 2008年3月1日
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Circulation journal : official journal of the Japanese Circulation Society 72 158-158 2008年3月1日
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Circulation journal : official journal of the Japanese Circulation Society 72 157-157 2008年3月1日
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Circulation journal : official journal of the Japanese Circulation Society 72 70-70 2008年3月1日
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Circulation journal : official journal of the Japanese Circulation Society 72 713-714 2008年3月1日
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Circulation journal : official journal of the Japanese Circulation Society 72 354-354 2008年3月1日
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Circulation journal : official journal of the Japanese Circulation Society 72 256-256 2008年3月1日
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Circulation journal : official journal of the Japanese Circulation Society 72 261-261 2008年3月1日
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Circulation journal : official journal of the Japanese Circulation Society 72 367-368 2008年3月1日
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Circulation journal : official journal of the Japanese Circulation Society 72 385-385 2008年3月1日
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Circulation journal : official journal of the Japanese Circulation Society 72 224-224 2008年3月1日
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Circulation journal : official journal of the Japanese Circulation Society 72 224-225 2008年3月1日
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Circulation journal : official journal of the Japanese Circulation Society 72 223-223 2008年3月1日
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