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
1923-
Japanese circulation journal 59(7) 510-510 1995年6月20日
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Japanese circulation journal 59(7) 385-385 1995年6月20日
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Japanese circulation journal 59(7) 393-393 1995年6月20日
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Japanese circulation journal 59(7) 393-393 1995年6月20日
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Japanese circulation journal 59 1995年6月20日
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BRAIN RESEARCH 682(1-2) 212-214 1995年6月We immunocytochemically stained the bovine brain with monoclonal antibodies against 155 kDa MLCK and myosin heavy chain (MHC) and a polyclonal antibody against calmodulin. In the bovine brain, a strong immunoreactivity with the anti-MLCK antibody was observed in neurons in all layers of the cerebral cortex and basal ganglia, and astrocytes in the white matter. The antibody also stained Purkinje, granular and molecular cells in the cerebellum. An anti MHC antibody stained neurons and astrocytes in the cerebral cortex and Purkinje cells similarly to the anti-MLCK antibody, whereas the MHC immunoreactivity was detected in the cerebellar glomerulus and there was no immunostaining of MHC in the granular and outer stellate cells. These results suggest that the 155 kDa MLCK might be related not only to the Ca-calmodulin-myosin system but also other intracellular system.
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心臓 27(5) 462-465 1995年5月圧負荷や炎症による障害を受けた心筋は心筋細胞形質を変換し,収縮装置やカルシウム制御蛋白の分子種のスイッチングや量を変化させる.収縮装置の変化としては,心筋ミオシンのα アイソフォームからβ アイソフォームへの変換,カルシウム制御機構の変化としては,粗面小胞体のCa2+-ATPaseの遺伝子発現の減弱(カルシウムポンプ数の減少)などがあげられる.このような変化を起こす細胞内シグナルとして,リン酸化カスケードや心筋内レニン・アンギオテンシン系の役割が注目されており,in vitro心筋細胞ストレッチングによる細胞内情報伝達系の解析,あるいは高血圧自然発症ラットの心肥大に対するアンギオテンシン変換酵素阻害薬やアンギオテンシンII受容体拮抗薬の効果などから,解明されてきた.
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Genomics 27(1) 204-6 1995年5月1日 査読有りHomeobox-containing genes play critical roles in regulating tissue-specific gene expression essential for tissue differentiation, as well as determining the temporal and spatial patterns of development. Recently, a human cardiac homeobox-containing gene, CSX, has been isolated. CSX is abundantly expressed in the human heart from fetal stages, suggesting that CSX plays an important role in human heart formation. In the present study, we have determined the chromosomal localization of CSX by fluorescence in situ hybridization techniques and systemic screening of a yeast artificial chromosome library using polymerase chain reaction. By these methods, CSX was mapped to 5q34 of human chromosome 5 near the boundary of 5q34 and 5q35. In this region, another homeobox-containing gene MSX2, which is expressed in various tissues including the conduction system of the developing heart, has been assigned. Localization of CSX and MSX2 to the same region of the human chromosome suggests that these genes may be coordinately regulated during human heart formation.
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European heart journal 16 Suppl C((supplC)) 8-11 1995年5月 査読有りMechanical stress induces cardiac hypertrophy and expression of specific genes in the cardiac myocytes. External stimuli are generally transduced into the nucleus through the activation of a protein kinase cascade. We have previously shown that stretching cardiomyocytes stimulates the activity of protein kinase C (PKC), mitogen-activated protein (MAP) kinase and S6 protein kinase. In the present study, we examined two other kinases, Raf-1 kinase and MAP kinase kinase, which are supposed to lie between PKC and MAP kinase in the protein kinase cascade. Stretching cardiocytes by using the in vitro system induced hyperphosphorylation of Raf-1 kinase and activation of MAP kinase kinase. The protein kinases activated by mechanical stress are similar to those activated by growth factors. We examined the possible involvement of angiotensin II (Ang II) in the protein synthesis and gene expression induced by mechanical stress. CV11974, an Ang II-receptor antagonist, partially suppressed the increases in amino acid incorporation, c-fos gene expression and MAP kinase activity induced by stretching. These results suggest that a variety of protein kinases are activated by mechanical stress and that locally produced Ang II may in part play important roles in converting mechanical stimuli into biochemical signals.
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Herz 20(2) 109-17 1995年4月 査読有りIt is known that mechanical stress directly changes the conformation of the functional proteins, or directly activates enzymes such as phospholipase in the plasma membrane. The integrin-cytoskeleton complex may be an alternative candidate structure for a mechanoreceptor and a transducer. The cytoskeleton has been also shown to play an important role in secretion. Mechanical stress may stimulate the secretion of some cytokines or angiotensin II, which may generate multiple intracellular signals as a secondary event. External stimuli are generally transduced into the nucleus through the activation of protein kinase cascade. Stretching of cardiac myocytes stimulates the activity of PKC, Raf-1 kinase, MAP kinase kinase. MAP kinase and S6 kinase. In cardiac myocytes, mechanical stress directly induces gene expression as well as protein synthesis. Immediate early genes are first induced, and then fetal-type genes are reinduced. Both in hypertrophied hearts and in the experimental model of cardiac hypertrophy induced by pressure overload. Ca(2+)-ATPase content of cardiac myocytes is depressed. Reduced function of sarcoplasmic reticulum causes insufficient decrease of intracellular calcium in diastole and induces slowing of ventricular relaxation. In the interstitium of pressure overloaded hearts, the accumulation of collagen fiber is increased. The abnormal deposit leads to increased chamber stiffness and diastolic dysfunction. Furthermore, TGF-beta and tissue renin-angiotensin system are up-regulated in pressure overloaded hearts, both of which accelerate the interstitial fibrosis.
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Internal medicine (Tokyo, Japan) 34(4) 279-81 1995年4月
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Japanese circulation journal 59 449-449 1995年3月1日
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Japanese circulation journal 59 449-449 1995年3月1日
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Japanese circulation journal 59 82-82 1995年3月1日
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Japanese circulation journal 59 283-283 1995年3月1日
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Japanese circulation journal 59 115-115 1995年3月1日
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Japanese circulation journal 59 475-475 1995年3月1日
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Japanese circulation journal 59 521-521 1995年3月1日
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Japanese circulation journal 59 373-373 1995年3月1日
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Japanese circulation journal 59 221-221 1995年3月1日
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Transplantation proceedings 27(1) 370-1 1995年2月 査読有り
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Transplantation proceedings 27(1) 578-578 1995年2月 査読有り
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Lancet (London, England) 345(8943) 191-2 1995年1月21日 査読有り
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Annals of the New York Academy of Sciences 748 578-85 1995年1月17日 査読有り
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血圧 2(2) 138-144 1995年エンドセリン(ET)-1遺伝子欠損マウスより血管内皮細胞を培養した.ET-1を欠損した血管内皮細胞は正常の形態を呈し,アセチルLDLの取り込みも認めた.血清存在下でのET-1欠損血管内皮細胞の増殖は正常の血管内皮細胞と変化なかった.ETアイソフォームの代償的な発現はなかった.bigET-1からET-1への変換もその程度に差はなかった.これらの結果より,ET-1は血管内皮の形態,増殖,ET-1のプロセッシング機構の発現にとっては必須ではなく,ETアイソフォームは血管内皮細胞ではredunduntな発現はないことが示唆された
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Journal of atherosclerosis and thrombosis 2(1) 14-23 1995年 査読有りSmooth muscle myosin heavy chains (MHC) exist in multiple isoforms. Rabbit smooth muscle contain at least three types of MHC isoforms; SM1 (204 kDa), SM2 (200 kDa) and SMemb (200 kDa). SM1 and SM2 are specific to smooth muscle, but SMemb is a nonmuscle-type MHC abundantly expressed in the embryonic aorta and in activated mesenchymal cells. We previously reported that these three MHC isoforms are differentially expressed in rabbit during normal vascular development and in experimental arteriosclerosis and demonstrated that MHC isoforms are excellent markers for smooth muscle phenotype. In order to clarify the clinical significance of MHC isoforms, this article will focus on the expression of smooth muscle MHC isoforms in normally developing and atherosclerotic human arteries, especially in coronary arteries. We recently isolated and characterized three cDNA clones encoding human SM1, SM2, and SMemb. The expression of SM2 mRNA in the human fetal aorta was significantly lower as compared to SM1 mRNA but the ratio of SM2- to SM1-mRNA was increased after birth. SMemb mRNA in the aorta was decreased after birth. Immunohistologically, SM1 was constitutively positive from the fetal stage to adulthood in the apparently normal media of the aorta and coronary arteries, whereas SM2 was not detected in fetal arteries of early gestational stage. SM2 was recognized in well-differentiated smooth muscle after perinatal stage. In the human aorta or coronary arteries, unlike in rabbit, SMemb was detected even in the adult. Mild diffuse intimal thickening in the major coronary arteries of the young was found to be composed of smooth muscle cells, reacting equally to three antibodies for MHC isoforms. In thickened but non-atheromatous intima, the expression of well-differentiated smooth muscle-specific MHC (SM2) was reduced, especially in the deeper layer. With progression of atherosclerosis, intimal smooth muscle diminished the expression of not only SM2 but also SM1, whereas alpha-smooth muscle actin was well preserved. We conclude from these results that smooth muscle MHC isoforms are important molecular markers for studying human vascular smooth muscle cell differentiation as well as the cellular mechanisms of atherosclerosis.
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Journal of Smooth Muscle Research 31(6) 439-443 1995年
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