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
-
2014年
-
2014年
-
2014年
-
2012年
受賞
7-
2010年3月
-
2009年5月
-
2006年11月
-
2002年7月
論文
955-
IJC Heart & Vasculature 54 101507-101507 2024年10月
-
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.
-
International Journal of Cardiology: Cardiovascular Risk and Prevention 22 2024年9月The authors regret that the original version of the article incorrectly stated the study period as “April 2014 to March 2020" in both the Abstract and the Methods section. The correct study period should have been “April 2013 to March 2019". The authors would like to apologise for any inconvenience caused.
-
JACC: Advances 3(7) 2024年7月Background: The prognostic implications of persistent low-grade inflammation in patients with chronic coronary syndrome (CCS) are underexplored. The REAL-CAD (Randomized Evaluation of Aggressive or Moderate Lipid Lowering Therapy with Pitavastatin in Coronary Artery Disease) study demonstrated the benefit of higher intensity pitavastatin in Japanese patients with CCS. Objectives: This prespecified subanalysis of the REAL-CAD study aimed to assess the prognostic effect of the persistent low-grade inflammation represented by high-sensitivity C-reactive protein (hs-CRP) in CCS patients. Methods: The present analysis involved patients without events until 6 months after randomization and whose hs-CRP levels were available at baseline and 6 months (n = 10,460). The primary endpoint was the composite of cardiovascular mortality, myocardial infarction, stroke, and unstable angina hospitalization. Landmark analyses evaluated the prognostic impact of continuous inflammation in 4 groups based on the median levels of hs-CRP (0.5 mg/L for both) at baseline and 6 months. The 4 groups included patient with persistently low, elevated (increased), reduced, and persistently high hs-CRP. Results: Adjusted Cox proportional hazard analyses demonstrated an increased risk of the primary endpoint in the group with persistently high hs-CRP when compared to the group with persistently low hs-CRP as a reference (adjusted HR: 1.48, 95% CI: 1.18-1.89; P = 0.001), but with a similar risk in the group with elevated (HR: 1.07, 95% CI: 0.77-1.49, P = 0.68) and reduced (HR: 0.92; 95% CI: 0.66-1.27; P = 0.60) hs-CRP. Conclusions: The study shows that persistent low-grade inflammation is associated with poor outcomes and underscores the need to address residual inflammatory risk in CCS patients. (Randomized Evaluation of Aggressive or Moderate Lipid Lowering Therapy With Pitavastatin in Coronary Artery Disease [REAL-CAD]; NCT01042730)
-
JACC. Advances 3(7) 100996-100996 2024年7月BACKGROUND: The prognostic implications of persistent low-grade inflammation in patients with chronic coronary syndrome (CCS) are underexplored. The REAL-CAD (Randomized Evaluation of Aggressive or Moderate Lipid Lowering Therapy with Pitavastatin in Coronary Artery Disease) study demonstrated the benefit of higher intensity pitavastatin in Japanese patients with CCS. OBJECTIVES: This prespecified subanalysis of the REAL-CAD study aimed to assess the prognostic effect of the persistent low-grade inflammation represented by high-sensitivity C-reactive protein (hs-CRP) in CCS patients. METHODS: The present analysis involved patients without events until 6 months after randomization and whose hs-CRP levels were available at baseline and 6 months (n = 10,460). The primary endpoint was the composite of cardiovascular mortality, myocardial infarction, stroke, and unstable angina hospitalization. Landmark analyses evaluated the prognostic impact of continuous inflammation in 4 groups based on the median levels of hs-CRP (0.5 mg/L for both) at baseline and 6 months. The 4 groups included patient with persistently low, elevated (increased), reduced, and persistently high hs-CRP. RESULTS: Adjusted Cox proportional hazard analyses demonstrated an increased risk of the primary endpoint in the group with persistently high hs-CRP when compared to the group with persistently low hs-CRP as a reference (adjusted HR: 1.48, 95% CI: 1.18-1.89; P = 0.001), but with a similar risk in the group with elevated (HR: 1.07, 95% CI: 0.77-1.49, P = 0.68) and reduced (HR: 0.92; 95% CI: 0.66-1.27; P = 0.60) hs-CRP. CONCLUSIONS: The study shows that persistent low-grade inflammation is associated with poor outcomes and underscores the need to address residual inflammatory risk in CCS patients. (Randomized Evaluation of Aggressive or Moderate Lipid Lowering Therapy With Pitavastatin in Coronary Artery Disease [REAL-CAD]; NCT01042730).
MISC
1912-
CIRCULATION 140 2019年11月0
-
計算工学講演会論文集 = Proceedings of the Conference on Computational Engineering and Science / 日本計算工学会 編 24 6p 2019年5月
-
計算工学講演会論文集 = Proceedings of the Conference on Computational Engineering and Science / 日本計算工学会 編 24 6p 2019年5月
-
Progress in Cardiovascular Diseases 60(3) 435-449 2017年11月1日We have developed a multisensor home and ambulatory blood pressure (BP) monitoring system for monitoring 24-h central and brachial BP variability concurrent with physical activity (PA), temperature, and atmospheric pressure. The new BP monitoring system utilizes our recently developed biological and environmental signal monitoring Information Communication Technology/Internet of Things system, which can simultaneously monitor the environment (temperature, illumination, etc.) of different rooms in a house (entryway, bedroom, living room, bathing room, and toilet), and a wrist-type high-sensitivity actigraph for identifying the location of patients. By collecting both data on BP and environmental parameters, the system can assess the brachial and central hemodynamic BP reactivity profiles of patients, such as actisensitivity (BP change with PA), thermosensitivity (with temperature), and atmospheric sensitivity (with atmospheric pressure). We used this new system to monitor ambulatory BP variability in outpatients with one or more cardiovascular disease (CVD) risk factors both in summer and winter. Actisensitivity (the slope of the regression line of ambulatory BP against the log-physical activity) was higher in winter than summer. By multi-level analysis using the parameters monitored by this system, we estimated the ambulatory BPs under different conditions. The individual time-series big data collected by this system will contribute to anticipation medicine for CVD.
-
The Journal of clinical investigation 127(1) 14-23 2017年1月3日 査読有りThe finding of islet inflammation in type 2 diabetes (T2D) and its involvement in β cell dysfunction has further highlighted the significance of inflammation in metabolic diseases. The number of intra-islet macrophages is increased in T2D, and these cells are the main source of proinflammatory cytokines within islets. Multiple human studies of T2D have shown that targeting islet inflammation has the potential to be an effective therapeutic strategy. In this Review we provide an overview of the cellular and molecular mechanisms by which islet inflammation develops and causes β cell dysfunction. We also emphasize the regulation and roles of macrophage polarity shift within islets in the context of T2D pathology and β cell health, which may have broad translational implications for therapeutics aimed at improving islet function.
-
EUROPEAN HEART JOURNAL 37 907-908 2016年8月
-
Diabetes research and clinical practice 118 154-5 2016年8月 査読有り
-
日本小児循環器学会雑誌 32(Suppl.1) s1-124 2016年7月
-
EUROPEAN HEART JOURNAL 36 868-868 2015年8月
-
日本小児循環器学会雑誌 31(Suppl.1) s1-103 2015年7月
-
Nature communications 6 6332-6332 2015年3月10日 査読有りAlveolar macrophages play a crucial role in the pathogenesis of emphysema, for which there is currently no effective treatment. Bisphosphonates are widely used to treat osteoclast-mediated bone diseases. Here we show that delivery of the nitrogen-containing bisphosphonate alendronate via aerosol inhalation ameliorates elastase-induced emphysema in mice. Inhaled, but not orally ingested, alendronate inhibits airspace enlargement after elastase instillation, and induces apoptosis of macrophages in bronchoalveolar fluid via caspase-3- and mevalonate-dependent pathways. Cytometric analysis indicates that the F4/80(+)CD11b(high)CD11c(mild) population characterizing inflammatory macrophages, and the F4/80(+)CD11b(mild)CD11c(high) population defining resident alveolar macrophages take up substantial amounts of the bisphosphonate imaging agent OsteoSense680 after aerosol inhalation. We further show that alendronate inhibits macrophage migratory and phagocytotic activities and blunts the inflammatory response of alveolar macrophages by inhibiting nuclear factor-κB signalling. Given that the alendronate inhalation effectively induces apoptosis in both recruited and resident alveolar macrophages, we suggest this strategy may have therapeutic potential for the treatment of emphysema.
-
日本心臓血管外科学会雑誌 44(2) 1-21 2015年3月
-
Journal of cardiology 65(2) 150-6 2015年2月 査読有りBACKGROUND: Immunoglobulin G4 (IgG4)-related disease has been suggested to be involved in cardiovascular disorders such as chronic periaortitis. However, it remains unclear whether IgG4-related immuno-inflammation affects the subclinical stages of aortic remodeling. Here, we analyzed the relationship between serum IgG4 concentrations and the morphology of the ascending aorta. METHODS: Serum concentrations of IgG4 were measured in 322 patients who underwent 320-slice cardiac computed tomography (CT). We assessed the aortic wall area and intravascular area at the portion between the aortic valve and the bifurcation of the pulmonary artery. RESULTS: In total, 174 patients (54.0%) were diagnosed to have coronary artery disease (CAD) by cardiac CT. The intravascular area was significantly larger in patients with CAD than in those without (893mm(2) vs. 811mm(2), p=0.001). The aortic wall area was slightly, but not significantly, larger in patients with CAD than in those without (183mm(2) vs. 176mm(2), p=0.051). Serum concentrations of IgG4 were significantly higher in patients with an aortic wall area of median or greater size (≥181mm(2)) than in those with a smaller area (<181mm(2)) (32.9mg/dL vs. 23.1mg/dL, p=0.026). In logistic regression analysis using age, gender, and CAD as covariates, the fourth quartile of IgG4 (≥55.4mg/dL) was significantly associated with an aortic wall area of median or greater size with an odds ratio of 2.09. CONCLUSIONS: Serum concentrations of IgG4 were found to be significantly associated with the aortic wall area. These findings collectively suggest that immuno-inflammatory processes may play a role in the subclinical stages of aortic remodeling.
-
Nature communications 5 5797-5797 2014年12月12日 査読有りSystemic sclerosis (SSc) is manifested by fibrosis, vasculopathy and immune dysregulation. So far, a unifying hypothesis underpinning these pathological events remains unknown. Given that SSc is a multifactorial disease caused by both genetic and environmental factors, we focus on the two transcription factors, which modulate the fibrotic reaction and are epigenetically suppressed in SSc dermal fibroblasts, Friend leukaemia integration 1 (Fli1) and Krüppel-like factor 5 (KLF5). In addition to the Fli1 silencing-dependent collagen induction, the simultaneous knockdown of Fli1 and KLF5 synergistically enhances expression of connective tissue growth factor. Notably, mice with double heterozygous deficiency of Klf5 and Fli1 mimicking the epigenetic phenotype of SSc skin spontaneously recapitulate all the three features of SSc, including fibrosis and vasculopathy of the skin and lung, B-cell activation and autoantibody production. These studies implicate the epigenetic downregulation of Fli1 and KLF5 as a central event triggering the pathogenic triad of SSc.
-
Diabetes 63(12) 4154-64 2014年12月 査読有りBody weight is tightly regulated by food intake and energy dissipation, and obesity is related to decreased energy expenditure (EE). Herein, we show that nucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2, autotaxin) is an adipose-derived, secreted enzyme that controls adipose expansion, brown adipose tissue (BAT) function, and EE. In mice, Enpp2 was highly expressed in visceral white adipose tissue and BAT and is downregulated in hypertrophied adipocytes/adipose tissue. Enpp2(+/-) mice and adipocyte-specific Enpp2 knockout mice fed a high-fat diet showed smaller body weight gains and less insulin resistance than control mice fed the same diet. BAT was functionally more active and EE was increased in Enpp2-deficient mice. In humans, ENPP2 expression in subcutaneous fat and ENPP2 levels in serum were reduced in obese subjects. Taken together, our results establish ENPP2 as an adipose-derived, secreted enzyme that regulates adipose obesity and systemic metabolism. They also suggest ENPP2 could be a useful therapeutic target for the treatment of metabolic disease.
-
CIRCULATION 130 2014年11月
-
EUROPEAN HEART JOURNAL 35 1024-1024 2014年9月
-
INTERNATIONAL JOURNAL OF CARDIOLOGY 176(1) 303-303 2014年9月
-
JOURNAL OF THROMBOSIS AND HAEMOSTASIS 12 71-71 2014年6月
-
Morphological distinction unravels mechanisms of platelet biogenesis from bone marrow megakaryocytesJOURNAL OF THROMBOSIS AND HAEMOSTASIS 12 69-69 2014年6月
-
Cardiovascular research 102(2) 191-3 2014年5月1日 査読有り
-
Journal of molecular and cellular cardiology 70 64-73 2014年5月 査読有りUnder normal physiological conditions, cardiac fibroblasts are the primary producers of extracellular matrix and supply a mechanical scaffold for efficacious heart contractions induced by cardiomyocytes. In the hypertrophic heart, cardiac fibroblasts provide a pivotal contribution to cardiac remodeling. Many growth factors and extracellular matrix components secreted by cardiac fibroblasts induce and modify cardiomyocyte hypertrophy. Recent evidence revealed that cardiomyocyte-cardiac fibroblast communications are complex and multifactorial. Many growth factors and molecules contribute to cardiac hypertrophy via different roles that include induction of hypertrophy and the feedback hypertrophic response, fine-tuning of adaptive hypertrophy, limitation of left ventricular dilation, and modification of interstitial changes. This review focuses on recent work and topics and provides a mechanistic insight into cardiomyocyte-cardiac fibroblast communication in cardiac hypertrophy. This article is part of a Special Issue entitled "Myocyte-Fibroblast Signalling in Myocardium ".
-
Cardiovascular research 102(2) 232-9 2014年5月1日 査読有りThe heart is composed of several cell types including cardiomyocytes, cardiac fibroblasts, endothelial, and smooth muscle cells. In addition to these major cell types, cardiac macrophages are also present in small numbers under physiological conditions. Recently, the resident macrophage is considered to have vital functions in the maintenance of tissues and homeostasis in many organs, including brain, liver, adipose tissue, lymphatic tissue, and intestinal tract. However, detailed functions of the cardiac resident macrophage are not fully understood. Although the removal of debris arising from damaged cardiomyocytes and pro-inflammatory effects after heart injuries are conventional tasks of cardiac macrophages (classically activated macrophage or M1 macrophage), novel functions like anti-inflammatory roles, adaptive response, and tissue maintenance have also been reported in recent years. Macrophages that possess these novel functions are generally so-called M2 macrophages, which are alternatively activated and show anti-inflammatory phenotype under pathological conditions. In this review, we focus on the cardioprotective function of the cardiac macrophage and discuss in light of unveiled fundamental functions of macrophages that have been also found in other organs.
書籍等出版物
21-
Springer 2009年 (ISBN: 9784431877745)
-
Signal Transduction and Cardiac Hypertrophy (Naranjan S. Dhalla, Larry Hryshko, Elissavet Kardami, Pawan K. Singal, KLUWER ACADEMIC PUBLISHERS) 2003年
-
Signal Transduction and Cardiac Hypertrophy (Naranjan S. Dhalla, Larry Hryshko, Elissavet Kardami, Pawan K. Singal, KLUWER ACADEMIC PUBLISHERS) 2003年
-
Rapid Cycle Real-Time PCR : methods and applications 2001年
-
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
-
日本学術振興会 科学研究費助成事業 2020年7月 - 2023年3月
-
日本学術振興会 科学研究費助成事業 2019年4月 - 2023年3月
-
日本学術振興会 科学研究費助成事業 2019年4月 - 2023年3月
-
日本学術振興会 科学研究費助成事業 2018年6月 - 2023年3月