論文 - 海北 幸一
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Fukunaga T., Soejima H., Irie A., Fukushima R., Oe Y., Kawano H., Sumida H., Kaikita K., Sugiyama S., Nishimura Y., Ogawa H.
Circulation Journal 73 ( 10 ) 1914 - 1919 2009年10月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Circulation Journal
Background: Dendritic cells (DCs) stimulate T-cells to participate in the inflammatory processes that promote the destruction of vulnerable plaques. The relationship between circulating levels of myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) in patients with acute coronary syndrome (ACS) was evaluated. Methods and Results: Biood samples were obtained from 39 patients with ACS, 41 patients with stable angina pectoris (SAP) and 43 controls. The proportion of mDCs tended to be lower in the ACS group than in the SAP group and controls. Interleukin-12 levels associated with mDCs were significantly higher in the ACS group than in control group. The proportion of pDCs was significantly lower in the ACS groups than in the other two groups. Interferon-α levels secreted by pDCs, however, were not significantly different among the 3 groups. The ratio of mDCs to pDCs ≥4 is an important value for distinguishing ACS from SAP patients and control patients through receiver operating characteristic analysis (sensitivity; 85.0%, specificity; 83.4%). Conclusions: The ratio of mDCs to pDCs may be a useful marker for detecting ACS and the existence of vulnerable plaques.
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Tabata M., Kadomatsu T., Fukuhara S., Miyata K., Ito Y., Endo M., Urano T., Zhu H.J., Tsukano H., Tazume H., Kaikita K., Miyashita K., Iwawaki T., Shimabukuro M., Sakaguchi K., Ito T., Nakagata N., Yamada T., Katagiri H., Kasuga M., Ando Y., Ogawa H., Mochizuki N., Itoh H., Suda T., Oike Y.
Cell Metabolism 10 ( 3 ) 178 - 188 2009年9月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Cell Metabolism
Recent studies of obesity have provided new insights into the mechanisms underlying insulin resistance and metabolic dysregulation. Numerous efforts have been made to identify key regulators of obesity-linked adipose tissue inflammation and insulin resistance. We found that angiopoietin-like protein 2 (Angptl2) was secreted by adipose tissue and that its circulating level was closely related to adiposity, systemic insulin resistance, and inflammation in both mice and humans. Angptl2 activated an inflammatory cascade in endothelial cells via integrin signaling and induced chemotaxis of monocytes/macrophages. Constitutive Angptl2 activation in vivo induced inflammation of the vasculature characterized by abundant attachment of leukocytes to the vessel walls and increased permeability. Angptl2 deletion ameliorated adipose tissue inflammation and systemic insulin resistance in diet-induced obese mice. Conversely, Angptl2 overexpression in adipose tissue caused local inflammation and systemic insulin resistance in nonobese mice. Thus, Angptl2 is a key adipocyte-derived inflammatory mediator that links obesity to systemic insulin resistance. © 2009 Elsevier Inc. All rights reserved.
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Hokimoto S., Matsui K., Oshima S., Noda K., Kaikita K., Sumida H., Sugiyama S., Ogawa H.
Journal of Cardiology 54 ( 1 ) 71 - 75 2009年8月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Cardiology
Background: The aim of this study was to examine the effects of gastric medicines on gastroduodenal injury during antiplatelet therapy after coronary intervention. Methods: A total of 501 patients were enrolled and as dual antiplatelet therapy, aspirin and thienopyridine were administered. Patients were divided into four groups: histamine H2-receptor antagonists (H2RA); proton pump inhibitors (PPI); other gastromucosal protective agents (GMP); or nothing (None), and follow-up lasted 8-20 months. Results: H2RA were prescribed in 212 cases (42%), PPI in 150 (30%), GMP in 56 (11%), and None in 83 (17%). Significant findings by endoscopy were recognized in 18 cases and upper gastrointestinal bleeding requiring hospitalization occurred in 7 patients (1.4%; H2RA in 4, GMP in 2, and None in 1). There were no gastrointestinal injuries in the PPI group. To minimize the effect of selection bias on gastroduodenal lesions, the propensity score analysis for clinical characteristics was used. The results of propensity score matching showed that administration of PPI reduced the incidence of gastrointestinal lesions compared with that of the non-PPI group. Conclusion: Administration of PPI reduced the incidence of gastrointestinal lesions compared with that of the non-PPI group. © 2009 Japanese College of Cardiology.
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Uemura T., Kaikita K., Yamabe H., Soejima K., Matsukawa M., Fuchigami S., Tanaka Y., Morihisa K., Enomoto K., Sumida H., Sugiyama S., Ogawa H.
Thrombosis Research 124 ( 1 ) 28 - 32 2009年5月
担当区分：責任著者 記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Thrombosis Research
Introduction: Previous studies have shown raised plasma von Willebrand factor (VWF) levels in patients with atrial fibrillation (AF). However, little is known about changes of VWF associated with VWF-cleaving protease (ADAMTS13) in AF. The aim of this study was to examine the relationship between changes in plasma VWF and ADAMTS13 levels, and left atrial remodeling in AF patients. Materials and Methods: We measured plasma VWF and ADAMTS13 antigen levels in 70 paroxysmal AF (PAF) patients, 56 chronic AF (CAF) patients, and 55 control subjects. Results: Plasma VWF levels (mU/ml) were significantly higher in CAF and PAF patients compared with the controls (2103 ± 743, 1930 ± 676, 1532 ± 555, respectively, P < 0.0001 in CAF vs. controls, P = 0.001 in PAF vs. control), while ADAMTS13 levels (mU/ml) were significantly lower in CAF and PAF patients compared with the controls (795 ± 169, 860 ± 221, 932 ± 173, respectively, P = 0.0002 in CAF vs. controls, P = 0.04 in PAF vs. control). The VWF/ADAMTS13 ratio was significantly higher in patients with CAF than PAF or controls (2.81 ± 1.30, 2.34 ± 0.92, 1.73 ± 0.83, respectively; P = 0.01 in CAF vs. PAF, P < 0.0001 in CAF vs. controls). There was a significant correlation between the VWF/ADAMTS13 ratio and left atrial diameter (positive correlation; r = 0.275, P = 0.0002) and left atrial appendage flow velocity (negative correlation; r = - 0.345, P = 0.0018). Conclusions: These findings suggest that the imbalance between plasma VWF and ADAMTS13 levels caused by left atrial remodeling might be closely associated with intra-atrial thrombus formation in AF patients. © 2008 Elsevier Ltd. All rights reserved.
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Morihisa K., Yamabe H., Uemura T., Tanaka Y., Enomoto K., Kawano H., Nagayoshi Y., Kaikita K., Sumida H., Sugiyama S., Ogawa H.
PACE - Pacing and Clinical Electrophysiology 32 ( 4 ) 484 - 493 2009年4月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：PACE - Pacing and Clinical Electrophysiology
Background: The precise nature of the upper turnaround part of atrioventricular nodal reentrant tachycardia (AVNRT) is not entirely understood. Methods: In nine patients with AVNRT accompanied by variable ventriculoatrial (VA) conduction block, we examined the electrophysiologic characteristics of its upper common pathway. Results: Tachycardia was induced by atrial burst and/or extrastimulus followed by atrial-His jump, and the earliest atrial electrogram was observed at the His bundle site in all patients. Twelve incidents of VA block: Wenckebach VA block (n = 7), 2:1 VA block (n = 4), and intermittent (n = 1) were observed. In two of seven Wenckebach VA block, the retrograde earliest atrial activation site shifted from the His bundle site to coronary sinus ostium just before VA block. Prolongation of His-His interval occurred during VA block in 11 of 12 incidents. After isoproterenol administration, 1:1 VA conduction resumed in all patients. Catheter ablation at the right inferoparaseptum eliminated antegrade slow pathway conduction and rendered AVNRT noninducible in all patients. Conclusion: Selective elimination of the slow pathway conduction at the inferoparaseptal right atrium may suggest that the subatrial tissue linking the retrograde fast and antegrade slow pathways forms the upper common pathway in AVNRT with VA block. © 2009 Wiley Periodicals, Inc.
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Smoking cessation is associated with increased plasma adiponectin levels in men 査読あり
Otsuka F., Kojima S., Maruyoshi H., Kojima S., Matsuzawa Y., Funahashi T., Kaikita K., Sugiyama S., Kimura K., Umemura S., Ogawa H.
Journal of Cardiology 53 ( 2 ) 219 - 225 2009年4月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Cardiology
Objectives: Low levels of adiponectin, an adipocytokine with anti-diabetic and anti-atherogenic properties, are associated with increased risk of future myocardial infarction in men. Previous studies have demonstrated that cigarette smoking is involved in the development of insulin resistance, and current smokers have been shown to have reduced plasma adiponectin levels. However, the influence of smoking cessation on adiponectin levels remains unknown. We sought to assess whether smoking cessation is associated with increased plasma adiponectin levels in men. Methods: The study includes 72 men (47 non-smokers and 25 current smokers at baseline) with stable angina pectoris who underwent percutaneous coronary intervention and follow-up coronary angiography 6 months later. During the 6-month follow-up period, all 47 non-smokers remained non-smokers, while 15 men of the 25 baseline current smokers successfully quit smoking. We evaluated plasma adiponectin levels at coronary intervention and 6 months later. Results: Plasma adiponectin levels at coronary intervention were comparable to those after 6 months in non-smokers (4.22 [3.15-6.43] vs. 4.58 [3.03-6.26] μg/mL, P = 0.124) and in persistent smokers (4.77 [4.25-10.53] vs. 5.16 [4.11-8.10] μg/mL, P = 0.721). Meanwhile, an increase in adiponectin level was observed in patients who quit smoking for 6 months (4.24 [3.30-5.70] vs. 5.50 [4.03-8.00] μg/mL, P = 0.002). Univariate analysis revealed that the percent increase in adiponectin levels correlated positively with smoking cessation (P = 0.003) and negatively with additional use of β-blockers (P = 0.049). In addition, increases in adiponectin levels were closely associated with increase in high-density lipoprotein cholesterol (P = 0.148), decrease in triglycerides (P = 0.140), and additional use of renin-angiotensin system inhibitors (P = 0.069). Multivariate analysis demonstrated that smoking cessation was an independent determinant of the increase in adiponectin (P = 0.036). Conclusions: Smoking cessation is associated with increased plasma adiponectin levels in men with stable angina, suggesting that the significance of smoking cessation may be partly explained by the increase in adiponectin level. © 2008 Japanese College of Cardiology.
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Effects of imidapril therapy on endogenous fibrinolysis in patients with recent myocardial infarction 査読あり
Soejima H, Ogawa H＊, Yasue H, Suefuji H, Kaikita K
Clinical Cardiology 20 ( 5 ) 441 - 445 2009年2月
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Sugamura K., Sugiyama S., Nozaki T., Matsuzawa Y., Izumiya Y., Miyata K., Nakayama M., Kaikita K., Obata T., Takeya M., Ogawa H.
Circulation 119 ( 1 ) 28 - 36 2009年1月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Circulation
Cannabinoid 1 (CB1) receptor blockade with rimonabant represents a clinical therapeutic strategy for obesity. Recently, the role of the endocannabinoid system has been described in peripheral organs. We sought to determine whether the endocannabinoid system could be involved in human atherosclerosis and whether CB1 receptor blockade could modulate proinflammatory activity in macrophages. Methods and Results-mRNA expression levels of CB1 receptor in coronary atherectomy samples were significantly higher in patients with unstable angina than in those with stable angina (3.62±2.96-fold; n=7; P<0.05). Immunoreactive area analysis of the coronary artery showed that CB1 receptor expression was greater in lipid-rich atheromatous plaques than in fibrous plaques, especially in CD68 macrophages (9.5± 1.2% versus 0.6±0.6%; n=5; P<0.01). Levels of blood endocannabinoids were significantly higher in patients with coronary artery disease (n=20) than those without coronary artery disease (n=20) (median [interquartile range]: anandamide, 1.048 pmol/mL [0.687 to 1.387 pmol/mL] versus 0.537 pmol/mL [0.468 to 0.857 pmol/mL], P<0.01; 2-arachidonoyl glycerol, 13.30 pmol/mL [6.65 to 16.21 pmol/mL] versus 7.67 pmol/mL [6.39 to 10.03 pmol/mL], P<0.05). In cultured macrophages, expression of CB1 receptor was significantly increased during monocyte-macrophage differentiation (1.78±0.13-fold; n=6; P<0.01). CB1 receptor blockade in macrophages induced a significant increase in cytosolic cAMP (29.9± 13.0%; n=4; P<0.01), inhibited phosphorylation of c-Jun N-terminal kinase (-19.1±12.6%, n=4; P<0.05), and resulted in a significant decrease in the production of proinflammatory mediators (interleukin-lβ, -28.9± 10.9%; interleukin-6, -24.8±7.6%; interleukin-8, -22.7±5.2%; tumor necrosis factor-α, -13.6±4.8%; matrix metalloproteinase-9, -16.4±3.8%; n=4 to 8; P<0.01). Conclusions-Patients with coronary artery disease demonstrated the activation of the endocannabinoid system with elevated levels of blood endocannabinoids and increased expression of CB1 receptor in coronary atheroma. CB1 receptor blockade exhibited antiinflammatory effects on macrophages, which might provide beneficial effects on atherogenesis. (Circulation. 2009;119:28-36.) © 2009 American Heart Association, Inc.
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致死性不整脈を伴った特発性心室瘤の2症例 査読あり
森久 健二, 角田 等, 杉山 正悟, 小川 久雄, 山部 浩茂, 榎本 耕治, 上村 孝史, 田中 靖章, 松澤 泰志, 永吉 靖央, 海北 幸一, 河野 宏明
心臓 41 ( 9 ) 1012 - 1017 2009年
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：公益財団法人 日本心臓財団
症例1: 69歳, 女性. 胸痛, 嘔吐の後, 意識消失し救急車で近医に搬入. 心電図は心拍数180/分のwide QRS tachycardiaでありlidocaine 100mg静注で頻拍は停止. 心エコーで左室後基部に菲薄化, 壁運動の低下を認め, 精査目的で当院に転院. Ergonovine負荷を含めた冠動脈造影で有意な所見はなく, 左室造影で後壁基部に瘤を認めた. 電気生理学的検査(EPS) では心拍数260/分, 210/分および200/分の3種類の心室頻拍が誘発され, 頻拍により血行動態が破綻したためカテーテルアブレーションは施行せず, 植込み型除細動器(implantable cardioveter defibrillator; ICD) 植え込みを行った.<BR>症例2: 68歳, 男性. ソフトボールの試合中に守備についていたところ突然意識消失. 救急車を要請し, 救急隊到着時の自動体外式除細動器(automated external defibrillator; AED)で心室細動が確認され, 除細動を施行し洞調律に復した. 冠動脈造影では有意狭窄はなく, 左室造影では後壁基部に瘤を認めた. EPSでは心室頻拍, 心室細動は誘発されなかったが, 運動負荷検査で心拍数220/分の持続性心室頻拍が誘発された. 致死性不整脈の2次予防目的でICD植え込みを行った. 2症例とも心臓カテーテル検査, 血液検査, 心筋シンチグラフィなどからは心室瘤の原因は特定できず, 特発性心室瘤が原因で致死性不整脈をきたしたものと考えられた.
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Uemura T., Yamabe H., Tanaka Y., Morihisa K., Kawano H., Kaikita K., Sumida H., Sugiyama S., Ogawa H.
Internal Medicine 47 ( 20 ) 1799 - 1802 2008年11月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Internal Medicine
Ventricular tachycardia originating from the right ventricular outflow tract (RVOT) is considered benign, but sometimes it causes polymorphic ventricular tachycardia and ventricular fibrillation, resulting in sudden cardiac death. A 58-year-old woman without structural heart disease was admitted for evaluation of recurrent episodes of syncope. Surface ECG showed frequent repetitive premature ventricular contraction (PVC) of RVOT origin. Polymorphic ventricular tachycardia triggered by the same PVC was documented by Holter ECG during an episode of syncope. Radiofrequency catheter ablation was performed to eradicate this PVC. No polymorphic ventricular tachycardia has developed after the procedure, and the patient has had no recurrence of syncope. © 2008 The Japanese Society of Internal Medicine.
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冠攣縮性狭心症の診断と治療に関するガイドライン
小川久雄, 赤阪隆史, 奥村謙, 川嶋成乃亮, 川筋道雄, 木村一雄, 斎藤穎, 下川宏明, 末田章三, 嶽山陽一, 田辺恭彦, 土橋和文, 野出孝一, 服部隆一, 水野杏一, 三羽邦久, 室原豊明, 毛利正博, 山岸正和, 吉村道博, 井上晃男, 雪吹周生, 大下晃, 海北幸一, 河野宏明, 小島淳, 小菅雅美, 副島弘文, 財田滋穂, 中山雅文, 安田聡, 岸田浩, 友池仁暢, 土師一夫, 横山光宏.
Circulation journal 72 1195 - 1252 2008年11月
掲載種別：研究論文（学術雑誌）
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Ueno H., Nakayama M., Kojima S., Kusuhara K., Nagayoshi Y., Yamamuro M., Nishijima T., Usuku H., Kaikita K., Sumida H., Yamabe H., Sugiyama S., Yoshimura M., Ogawa H.
Heart and Vessels 23 ( 4 ) 243 - 248 2008年7月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Heart and Vessels
The prevalence of anemia in patients with heart failure (HF) increases according to disease severity as a consequence of renal insufficiency, cytokine production, plasma volume expansion, and/or malnutrition. B-type natriuretic peptide (BNP) has been recognized as a biochemical marker of ventricular dysfunction. The aim of this study was to evaluate the clinical significance of anemia in HF patients and furthermore, to investigate whether a significant correlation exists between anemia, BNP, and poor clinical outcomes in HF patients. We studied 185 consecutive HF patients. We assessed the occurrence of major adverse cardiac events (MACE) post hospital discharge. Anemia was defined as Hb concentrations <12.9 g/dl in men and <11.3 g/dl in women, respectively. Kaplan-Meier analysis revealed that anemia and high BNP levels (>259 pg/ml) were significantly associated with the occurrence of MACE. Multiple logistic analysis revealed that the most predictive independent risk factor for the occurrence of MACE was high BNP levels, followed by anemia (relative risk [RR] = 2.803 and 2.241, respectively). We divided the patients with or without anemia and high or low BNP levels into four groups according to their respective Hb and BNP levels. The hazard ratio for MACE in the group with anemia and high BNP levels was 10.3 in comparison to the group without anemia and with low BNP levels (P = 0.0002). Both anemia and high plasma levels of BNP are significantly and independently associated with the occurrence of MACE in HF patients; furthermore, the synergistic effect of anemia combined with high BNP levels significantly predicts an enhanced risk for MACE. © Springer Japan 2008.
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Nakayama M., Kudoh T., Kaikita K., Yoshimura M., Oshima S., Miyamoto Y., Takeya M., Ogawa H.
Atherosclerosis 198 ( 2 ) 426 - 433 2008年6月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Atherosclerosis
Objective: Morbidity and mortality rates are still high among patients with acute coronary syndrome (ACS); moreover, it is clinically difficult to determine precisely which patients will progress satisfactorily. Unstable plaque is characterized by an increased number of activated inflammatory cells, including macrophages and lymphocytes, and an increased release of numerous inflammatory mediators and proteolytic enzymes. Mononuclear cells consist of monocytes/macrophages and lymphocytes and are able to be experimentally isolated. We searched for a specific risk factor for ACS in the peripheral blood mononuclear cells (PBMCs). Methods and results: We examined the expression of 12,625 genes in PBMCs utilizing a gene chip microarray system in ACS patients in acute and chronic stable phases. The gene expression profiles revealed that class A macrophage scavenger receptors (SR-A), among the immune response factors and the receptor activity markers, were the most strongly increased in the acute phase. We examined SR-A gene expression levels of PBMCs using real time RT-PCR in 122 consecutive patients: 32 ACS patients; 41 stable angina patients; and, 49 control subjects. The SR-A gene expression levels of the PBMCs were highest in the ACS patients (p < 0.0001). The occurrence of a reattack of a cardiovascular event was significantly lower in the low SR-A group than in the high SR-A group (p < 0.001). Conclusion: SR-A gene expression level in the PBMCs specifically increases in patients with ACS, and provides a predictive marker for a reattack of a cardiovascular event. © 2007 Elsevier Ireland Ltd. All rights reserved.
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Honda T., Kaikita K., Tsujita K., Hayasaki T., Matsukawa M., Fuchigami S., Sugiyama S., Sakashita N., Ogawa H., Takeya M.
Journal of Molecular and Cellular Cardiology 44 ( 5 ) 915 - 926 2008年5月
担当区分：責任著者 記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Molecular and Cellular Cardiology
Although considerable attention has focused on obesity, insulin resistance and abnormal lipid metabolism as coronary risk factors, it remains unclear how these pathogenic factors affect the inflammatory response after myocardial ischemia-reperfusion. This study was conducted to evaluate whether these metabolic disorders exacerbate myocardial ischemia-reperfusion injury, and to determine if ischemia-reperfusion injury could be modified with the thiazolidinedione, pioglitazone. Experiments were performed in KK-A and C57BL/6J mice subjected to 40 min of ischemia followed by reperfusion. Infiltration of inflammatory cells in ischemic myocardium, and infarct size 3 days after reperfusion were significantly higher in KK-A than C57BL/6J mice (p < 0.05 and p < 0.001, respectively). Furthermore, expression of chemokines, inflammatory cytokines and extracellular matrix proteins in ischemic myocardium was significantly higher in KK-A than C57BL/6J mice 1 day after reperfusion. Pioglitazone treatment of KK-A mice for 14 days significantly reduced the accumulation of inflammatory cells in ischemic myocardium, and infarct size 3 days after reperfusion compared to vehicle treatment (p < 0.05 and p < 0.05, respectively). Pioglitazone also attenuated expression of chemokines, inflammatory cytokines and extracellular matrix proteins in ischemic myocardium 1 day after reperfusion. In vitro experiments demonstrated that tumor necrosis factor-α (TNF-α) was significantly higher in cultured peritoneal macrophages from KK-A than C57BL/6J mice, and pioglitazone significantly reduced TNF-α in macrophages from both types of mice. These findings suggest that metabolic disorders exacerbate ischemia-reperfusion injury as a result of overexpression of inflammatory mediators, and this effect might be improved, in part by the anti-inflammatory effects of pioglitazone. © 2008 Elsevier Inc. All rights reserved. y y y y y
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HDLコレステロールやLDLコレステロールは冠動脈内プラークの体積や組成を反映する.
小島淳, 小島志乃ぶ, 永吉靖央, 海北幸一, 角田等, 杉山正悟, 小川久雄.
超音波医学 35 S256 2008年4月
掲載種別：研究論文（学術雑誌）
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Fuchigami S., Kaikita K., Soejima K., Matsukawa M., Honda T., Tsujita K., Nagayoshi Y., Kojima S., Nakagaki T., Sugiyama S., Ogawa H.
Thrombosis Research 122 ( 5 ) 618 - 623 2008年2月
担当区分：責任著者 記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Thrombosis Research
Introduction: Increased plasma levels of von Willebrand factor (VWF) have been reported in acute myocardial infarction (AMI). Recently, we showed reduced activity of a VWF-cleaving protease (ADAMTS13) in AMI patients. However, there is no information as to whether ADAMTS13 affects the pathogenesis of unstable angina (UA). Thus, the purpose of this study was to examine changes in plasma VWF and ADAMTS13 levels in UA patients. Materials and methods: Plasma VWF and ADAMTS13 levels (mU/ml) were measured in 45 patients with UA, 55 with stable exertional angina (SEA) and 47 with chest pain syndrome (CPS) at the time of coronary angiography. Levels were also measured in 15 UA patients after 6 months of follow-up. Results: VWF antigen levels (mU/ml) increased significantly in UA patients compared with SEA or CPS (2129.3 ± 739.5, 1571.8 ± 494.2 and 1569.5 ± 487.0, respectively; P < 0.0001 in UA vs. SEA or CPS). ADAMTS13 antigen levels (mU/ml) were significantly lower in UA patients than SEA or CPS (737.3 ± 149.5, 875.3 ± 229.0 and 867.7 ± 195.5, respectively; P < 0.01 in UA vs. SEA or CPS). Furthermore, there was a significant inverse correlation between VWF and ADAMTS13 antigen levels (r = -0.302, P = 0.0002). The antigen levels at 6 months of follow-up were not different compared to the acute phase in the 15 UA patients that had repeated blood sampling. Conclusions: These findings suggest that there is prolonged thrombogenicity in UA patients represented as an imbalance between VWF and ADAMTS13 activity. © 2008 Elsevier Ltd. All rights reserved.
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Soejima H., Irie A., Fukunaga T., Oe Y., Kojima S., Kaikita K., Kawano H., Sugiyama S., Yoshimura M., Kishikawa H., Nishimura Y., Ogawa H.
Circulation Journal 71 ( 12 ) 1879 - 1884 2007年12月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Circulation Journal
Background: T cells in peripheral blood reflect the systemic inflammatory response in patients with heart failure (HF). In a rat model of HF, osteopontin is dramatically increased in the left ventricular myocardium, so the association between osteopontin and HF was examined in the present study. Methods and Results: Peripheral blood was collected from 93 patients with heart disease and 38 controls. Left ventricular ejection fraction (LVEF) was calculated using a modified Simpson's rule. The 93 patients were classified into 3 classes according to the New York Heart Association (NYHA) functional classification. Osteopontin-expressing CD4 T cells were quantified by flow cytometry. Plasma osteopontin levels (ng/ml) and the frequencies of osteopontin-expressing CD4 T cells (%) were higher in patients with HF than in controls (800±554, 575±229, p=0.016 and 27.3±12.2, 16.7±10.0, p<0.001). Furthermore, the plasma osteopontin levels and the frequencies of osteopontin-expressing CD4 T cells increased in proportion to the severity of the NYHA functional class. The frequencies of osteopontin-expressing CD4 T cells were significantly correlated with LVEF (r=-0.336, p=0.0048) and log plasma brain natriuretic peptide levels (r=0.305, p=0.0025). Conclusions: Osteopontin expression of circulating CD4 T cells and plasma osteopontin levels reflect the severity of HF. Osteopontin could be a new target in the assessment of HF. + + + + +
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血液バイオマーカーからのアプローチ
海北幸一、小川久雄
細胞 39 ( 14 ) 590 - 593 2007年12月
担当区分：筆頭著者 掲載種別：研究論文（学術雑誌）
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Suzuki S., Yoshimura M., Nakayama M., Abe K., Yamamuro M., Nagayoshi Y., Kojima S., Kaikita K., Sugiyama S., Yasue H., Ogawa H.
Pharmacogenetics and Genomics 17 ( 11 ) 919 - 930 2007年11月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Pharmacogenetics and Genomics
OBJECTIVE: Coronary spasm plays an important role in the pathogenesis of variant angina and also ischemic heart diseases in general, and it is more likely to occur in angiographically normal coronary arteries than in stenotic coronary arteries. We previously found a -786T/C polymorphism in the 5′-flanking region of the endothelial nitric oxide synthase (eNOS) gene and reported that this polymorphism is associated with coronary spasm. We report on an investigation of the genetic factor(s) associated with coronary spasm utilizing a genome-wide case-control study. METHODS AND RESULTS: We recruited 411 consecutive Japanese women (201 with coronary spasm; 210 controls) who were all underwent an acetylcholine provocation test. For single nucleotide polymorphism analysis (SNP), 116 204 SNPs were genotyped for 100 women (50 with coronary spasm; 50 controls) utilizing the Affymetrix GeneChip 100 K Set. Case-control studies were performed with 311 women (151 with coronary spasm; 160 controls) using the 10 lowest permutation P value SNPs from the initial SNP analysis. Finally, we discovered SNP rs10498345, a genetic marker for coronary spasm in Japanese women (Odds ratio=0.43, P=9.48×10). Haplotype analysis showed that haplotype H2, the only haplotype containing the protective A allele at SNP rs10498345, was most strongly associated with coronary spasm (permutation P value <1×10). SNP rs10498345 was strongly associated with the vasoconstrictor response to acetylcholine. Northern blot analysis revealed a novel 4.7 kb RNA transcript, which lacked poly (A), nearby SNP rs10498345. CONCLUSIONS: SNP rs10498345 was strongly associated with coronary spasm in Japanese women utilizing genome-wide SNP analysis. © 2007 Lippincott Williams & Wilkins, Inc.
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Matsukawa M., Kaikita K., Soejima K., Fuchigami S., Nakamura Y., Honda T., Tsujita K., Nagayoshi Y., Kojima S., Shimomura H., Sugiyama S., Fujimoto K., Yoshimura M., Nakagaki T., Ogawa H.
American Journal of Cardiology 100 ( 5 ) 758 - 763 2007年9月
担当区分：責任著者 記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：American Journal of Cardiology
Von Willebrand factor (VWF), a cofactor in platelet adhesion and aggregation, increases hemostasis and thrombosis. Recently, a metalloprotease that cleaves VWF multimers has been identified, namely ADAMTS13. The aim of this study was to investigate the relation between serial changes in plasma VWF and ADAMTS13 and the prognosis after acute myocardial infarction (AMI). We measured serial changes of plasma VWF and ADAMTS13 antigen levels in 92 patients with AMI and 40 control subjects. VWF levels were significantly higher in patients with AMI compared with controls (p <0.01) on admission, peaked 3 days after admission, and remained high for 14 days. In contrast, on admission, ADAMTS13 levels were significantly lower in patients with AMI compared with controls (p <0.0001), with minimum antigen levels reached after 3 days, and remained lower for 14 days. The ratio of VWF/ADAMTS13 antigen levels was higher in patients with AMI compared with controls throughout the time course. Cox hazards analysis revealed that the early increase of VWF and VWF/ADAMTS13 ratio levels and the early decrease of ADAMTS13 levels were significant predictors of future thrombotic events during the 1-year follow-up period. Kaplan-Meier analysis demonstrated that patients with major decreases of ADAMTS13 levels and high increases of VWF/ADAMTS13 levels had significantly greater probabilities for development of thrombotic events (p = 0.0104 and 0.0209, respectively). In conclusion, these findings suggest that monitoring the changes of VWF and ADAMTS13 antigen levels in the early phase might be valuable for predicting and preventing thrombosis during 1-year follow-up in patients with AMI. © 2007 Elsevier Inc. All rights reserved.