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-
DIABETOLOGIA 42 A103-A103 1999年8月
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BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 261(2) 332-339 1999年8月
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APPLIED RADIATION AND ISOTOPES 51(2) 197-202 1999年8月
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Angiology 50(8) 683-7 1999年8月 査読有り
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FEBS letters 456(1) 103-7 1999年7月30日 査読有り
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Circulation research 85(2) 182-91 1999年7月23日 査読有りWe have recently characterized the promoter region of the rabbit embryonic smooth muscle myosin heavy chain (SMemb/NMHC-B) gene and identified the 15-bp sequence, designated SE1, located at -105 from the transcriptional start site as an important regulatory element for its transcriptional activity in a smooth muscle cell (SMC) line. In this study, we attempted to isolate cDNA clones encoding for the transcription factors that control the expression of the SMemb gene through binding to this cis-regulatory element. We screened a lambdagt11 cDNA library prepared from C2/2 cells, a rabbit-derived SMC line, by using a radiolabeled concatenated oligonucleotide containing SE1 as a probe. Sequence analysis revealed that one of the cDNA clones corresponds to the rabbit homologue of basic transcriptional element binding protein-2 (BTEB2), which has previously been identified as one of the Krüppel-like transcription factor. Gel mobility shift assays and antibody supershift analyses with nuclear extracts from C2/2 cells indicate that BTEB2 is a major component of nuclear factor:SE1 complexes. Furthermore, a glutathione S-transferase-BTEB2 fusion protein binds to the SE1 in a sequence-specific manner. In support of the functionality of BTEB2 binding, basal promoter activity and BTEB2-induced transcriptional activation were markedly attenuated by the disruption of the SE1. In adult rabbit tissues, BTEB2 mRNA was most highly expressed in intestine, urinary bladder, and uterus. BTEB2 mRNA levels were downregulated in rabbit aorta during normal development. Moreover, immunohistochemical analysis indicated a marked induction of BTEB2 protein in the neointimal SMC after balloon injury in rat aorta. These results suggest that BTEB2 mediates the transcriptional regulation of the SMemb/NMHC-B gene and possibly plays a role in regulating gene expression during phenotypic modulation of vascular SMC.
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Cellular and molecular biology (Noisy-le-Grand, France) 45(5) 639-51 1999年7月 査読有り
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Journal of human hypertension 13(7) 437-42 1999年7月 査読有り
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JAPANESE CIRCULATION JOURNAL-ENGLISH EDITION 63(7) 572-575 1999年7月
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Angiology 50(7) 607-11 1999年7月 査読有り
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Japanese journal of pharmacology 80(2) 181-3 1999年6月We studied the role of nitric oxide (NO) synthesis in amelioration of blood pressure elevation during dietary salt loading in transgenic mice overexpressing sodium proton exchanger. Systolic blood pressure rose after starting salt loading only in the high-salt group of transgenic mice. However, this elevation of blood pressure was not continued. Urinary excretion of inorganic nitrite and nitrate in the high-salt group of transgenic mice was significantly higher than in the high-salt group of control mice. These results suggest that increased NO synthesis in response to salt loading is one of the anti-hypertensive mechanisms in transgenic mice overexpressing sodium proton exchanger.
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The American journal of physiology 276(6) H1968-76-H1976 1999年6月 査読有り
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EUROPEAN JOURNAL OF PHARMACOLOGY 374(3) 355-366 1999年6月
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脈管学 : 日本脈管学会機関誌 : the journal of Japanese College of Angiology 39(5) 237-241 1999年5月25日
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VIRCHOWS ARCHIV-AN INTERNATIONAL JOURNAL OF PATHOLOGY 434(5) 413-422 1999年5月
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東京女子医科大学雑誌 69(4) 164-169 1999年4月25日It has been well recognized that patients with major coronary risk factors develop atherosclerosis in a higher frequency, but there are many atherosclerotic patients without these risk factors, suggesting the presence of other unknown risk factors regulating development of atherosclerosis. It has been known that the most important risk factor for atherosclerosis is "aging" to whatever extent the major risk factors are involved in atherogenesis. We recently identified the klotho gene as a possible regulator of human aging process. Because endothelial function is impaired in aged subjects, it is plausible to hypothesize that klotho may protect against endothelial dysfunction. Therefore, we decided to examine whether the klotho-deficient mice have endothelial dysfunction. We first found that the klotho gene product itself or its metabolites protect against endothelial dysfunction as a humoral factor because endothelium-dependent arterial dilatation was impaired in the klotho-deficient heterozygous mouse, which was improved by establishing parabiosis with a wildtype mouse but not with a heterozygous mouse. Reduced expression of the klotho gene seems to be a risk factor of arterial diseases because heterozygous mouse with apparently normal histology of the arterial wall developed hypertension with high-salt drinking water and atherosclerosis with high cholesterol diet. We also have shown that in animal models of hypertension, kidney diseases, hyperlipidemia and diabetes, all of which are known as an important risk factor for atherosclerosis, klotho gene expression was reduced in kidney. It is noteworthy that endothelial dysfunction observed in a rat model of hyperlipidemia and hyperglycemia (OLETF rat) could be improved by angiotensin converting enzyme inhibitor, which is accompanied by increased klotho gene expression in kidney. Our results suggest that klotho gene expression is regulated by local or systemic stress against kidney or the vascular wall.
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JAPANESE CIRCULATION JOURNAL-ENGLISH EDITION 63(4) 274-277 1999年4月
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Archives of physical medicine and rehabilitation 80(4) 470-2 1999年4月 査読有り
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Japanese circulation journal 63(1) 655-655 1999年3月1日
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Japanese circulation journal 63(1) 654-654 1999年3月1日
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Japanese circulation journal 63(1) 656-656 1999年3月1日
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Japanese circulation journal 63(1) 302-302 1999年3月1日
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Japanese circulation journal 63(1) 460-460 1999年3月1日
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Japanese circulation journal 63(1) 249-249 1999年3月1日
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Japanese circulation journal 63(1) 344-344 1999年3月1日
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Japanese circulation journal 63(1) 349-349 1999年3月1日
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Japanese circulation journal 63(1) 313-313 1999年3月1日
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Japanese circulation journal 63(1) 426-426 1999年3月1日
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Japanese circulation journal 63(1) 378-378 1999年3月1日
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Japanese circulation journal 63(1) 183-183 1999年3月1日
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Japanese circulation journal 63(1) 187-187 1999年3月1日
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Japanese circulation journal 63(1) 183-183 1999年3月1日
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Japanese circulation journal 63(1) 182-182 1999年3月1日
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Japanese circulation journal 63(1) 105-105 1999年3月1日
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Japanese circulation journal 63(1) 105-105 1999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