論文 - 海北 幸一
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Honda T., Sugiyama S., Sakamoto T., Kaikita K., Ogawa H.
Circulation Journal 71 ( 8 ) 1263 - 1267 2007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：Circulation Journal
Background: Patients with hypertrophic cardiomyopathy (HCM) frequently complain of angina-like symptoms in the absence of organic coronary stenoses. Coronary spasm might cause myocardial ischemia in HCM patients. Delta-sarcoglycan plays a crucial role in the pathogenesis of HCM and coronary spasm in a mouse model. Methods and Results: This is a retrospective, single-center study with a small sample size. Seventy patients with HCM underwent coronary angiography and received acetylcholine provocation test. Coronary risk factors and 5′-untranslated region (UTR) G to C polymorphism on delta-sarcoglycan gene (n=64) were evaluated in the HCM patients. In 31 (44.3%) of 70 HCM patients, coronary spasm was induced by the provocation. None of the coronary risk factors was significantly different between the coronary spasm group and the non-coronary spasm group. The 5′-UTR gene polymorphism was associated with the occurrence of coronary spasm with an additive effect on the coexistence (p=0.025). Multiple logistic regression analysis showed that the C allele of 5′-UTR polymorphism was a significant risk factor for coronary spasm in patients with HCM (odds ratio, 3.1; 95% confidence interval, 1.0 to 9.5; p=0.045) that was independent of traditional coronary risk factors. Conclusions: The 5′-UTR polymorphism on delta-sarcoglycan gene was associated with coronary spasm in Japanese patients with HCM.
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Fukunaga T., Soejima H., Irie A., Sugamura K., Oe Y., Tanaka T., Nagayoshi Y., Kaikita K., Sugiyama S., Yoshimura M., Nishimura Y., Ogawa H.
American Journal of Cardiology 100 ( 3 ) 483 - 488 2007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：American Journal of Cardiology
The percentage of CD4 T cells in blood is correlated with left ventricular dysfunction and decreased ejection fraction in heart disease. The aim of this study was to determine the relation between activation of CD4 T cells and New York Heart Association functional classes in chronic heart failure (HF) and differences in inflammatory activation between ischemic cardiomyopathy (IC) and idiopathic dilated cardiomyopathy (IDC). Blood samples were obtained from 47 patients with HF and 20 controls. Percentages of interferon-γ-positive CD4 T cells (representative type 1 T-helper cells) and interleukin-4-positive CD4 T cells (representative type 2 T-helper cells) were analyzed using 3-color flow cytometry. The proportion of interferon-γ-positive CD4 T cells was higher in patients with HF (28.96 ± 12.90%) than in controls (18.12 ± 5.28, p = 0.0006), but there was no difference in percentage of interleukin-4-positive CD4 T cells between the 2 groups. The proportion of interferon-γ-positive CD4 T cells and plasma B-type natriuretic peptide levels increased with worsening of New York Heart Association functional class in the IC and IDC groups. The proportion of interferon-γ-positive CD4 T cells in the IC group (33.88 ± 13.33%) was higher than in the IDC group (22.33 ± 8.88%, p = 0.002); however, plasma B-type natriuretic peptide levels were higher in the IDC group (358.0 pg/ml, 327.5 to 1,325.7) than in the IC group (82.7 pg/ml, 34.7 to 252.9, p = 0.019). In conclusion, we demonstrated pronounced type 1 T-helper cell activation in patients with HF in proportion to severity of HF and that the specificity of T-cell activation differs between patients with IC and those with IDC. © 2007 Elsevier Inc. All rights reserved. + + + + + + + +
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Tsujita K., Kaikita K., Hayasaki T., Honda T., Kobayashi H., Sakashita N., Suzuki H., Kodama T., Ogawa H., Takeya M.
Circulation 115 ( 14 ) 1904 - 1911 2007年4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：Circulation
BACKGROUND - Class A macrophage scavenger receptor (SR-A) is a macrophage-restricted multifunctional molecule that optimizes the inflammatory response by modulation of the activity of inflammatory cytokines. This study was conducted with SR-A-deficient (SR-A) mice to evaluate the relationship between SR-A and cardiac remodeling after myocardial infarction. METHODS AND RESULTS - Experimental myocardial infarction (MI) was produced by ligation of the left coronary artery in SR-A and wild-type (WT) male mice. The number of mice that died within 4 weeks after MI was significantly greater in SR-A mice than in WT mice (P=0.03). Importantly, death caused by cardiac rupture within 1 week after MI was 31% (17 of 54 mice) in SR-A mice and 12% (6 of 51 mice) in WT mice (P=0.01). In situ zymography demonstrated augmented gelatinolytic activity in the infarcted myocardium in SR-A mice compared with WT mice. Real-time reverse transcription-polymerase chain reaction at day 3 after MI showed that the expression of matrix metalloproteinase-9 mRNA increased significantly in the infarcted myocardium in SR-A mice compared with WT mice. Furthermore, SR-A mice showed augmented expression of tumor necrosis factor-α and reduction of interleukin-10 in the infarcted myocardium at day 3 after MI. In vitro experiments also demonstrated increased tumor necrosis factor-α and decreased interleukin-10 expression in activated SR-A macrophages. CONCLUSIONS - The present findings suggest that SR-A deficiency might cause impairment of infarct remodeling that results in cardiac rupture via insufficient production of interleukin-10 and enhanced expression of tumor necrosis factor-α and of matrix metalloproteinase-9. SR-A might contribute to the prevention of cardiac rupture after MI. © 2007 American Heart Association, Inc.
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Sugamura K., Sugiyama S., Kawano H., Horio E., Ono S., Kojima S., Kaikita K., Sagishima K., Sakamoto T., Yoshimura M., Kinoshita Y., Ogawa H.
Journal of Cardiology 48 ( 6 ) 345 - 352 2006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：Journal of Cardiology
A 20-year-old female survived fulminant myocarditis with 56 hr of non-responsive cardiac arrest and was able to resume a normal life with cardiac resynchronization therapy (CRT). On admission, she had developed cardiogenic shock refractory to pharmacological intervention. Percutaneous cardiopulmonary support was initiated with intraaortic balloon pumping. She developed complete cardiac standstill unresponsive to ventricular pacing. After 56 hr of cardiac arrest, ventricular fibrillation occurred and her ventricle started to respond to pacing therapy. She could leave the intensive care unit, although she continued to have severe heart failure refractory to medical intervention. She presented with paradoxical ventricular motion with a low cardiac output, so CRT was performed. After the initiation of CRT, her heart failure symptoms improved and she could return home.
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Okuma T., Terasaki Y., Sakashita N., Kaikita K., Kobayashi H., Hayasaki T., Kuziel W.A., Baba H., Takeya M.
International Journal of Experimental Pathology 87 ( 6 ) 475 - 483 2006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：International Journal of Experimental Pathology
To clarify the role of the monocyte chemoattractant protein-1 (MCP-1)/C-C chemokine receptor 2 (CCR2) signalling pathway in hyperoxia-induced acute lung injury, CCR2-deficient (CCR2-/-) and wild-type (CCR2+/+) mice were exposed to 85% O for up to 6 days. At day 3, body weight significantly decreased and total protein concentration in bronchoalveolar lavage fluid (BALF) was higher in CCR2-/- mice compared with CCR2+/+ mice. Cumulative survivals were significantly lower in CCR2-/- mice than in CCR2+/+ mice. However, the two groups showed no significant differences in both histological changes and number of macrophages in BALF. Real-time reverse transcriptase-polymerase chain reaction revealed increased mRNA levels of MCP-1, interleukin-1β thioredoxin-1, and inducible nitric oxide synthase (iNOS) in lung tissues in CCR2-/- mice compared with CCR2+/+ mice. Increased iNOS mRNA levels in alveolar macrophages exposed to 85% O for 48 h in vivo or in vitro were significantly higher in CCR2-/- mice than in CCR2+/+ mice. These results suggest that the MCP-1/CCR2 signalling pathway is protective against hyperoxia-induced tissue injury by suppressing induction of iNOS and consequent production of reactive oxygen species by activated alveolar macrophages. © 2006 Blackwell Publishing Ltd. 2 2
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Reduced von Willebrand factor-cleaving protease (ADAMTS13) activity in acute myocardial infarction 査読あり
Kaikita K＊, Soejima K, Matsukawa M, Nakagaki T, Ogawa H
J Thromb Haemost 4 ( 11 ) 2490 - 2493 2006年8月
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Long-term efficacy of edaravone in patients with acute myocardial infarction 査読あり
Tsujita K., Shimomura H., Kaikita K., Kawano H., Hokamaki J., Nagayoshi Y., Yamashita T., Fukuda M., Nakamura Y., Sakamoto T., Yoshimura M., Ogawa H.
Circulation Journal 70 ( 7 ) 832 - 837 2006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：Circulation Journal
Background: The effect of edaravone, a free radical scavenger, on long-term prognosis and its efficacy with regards to scavenging injurious free radicals in patients with acute myocardial infarction (AMI) was examined. Methods and Results: One hundred and one initial AMI patients were randomly assigned to receive 30 mg edaravone (n=50) or a placebo (n=51) intravenously just before reperfusion. The infarct size, using serum biomarkers and Q-wave formations, and the incidence of reperfusion arrhythmia between the groups were compared. Cardiovascular event-free curves were estimated by using the Kaplan-Meier method. In addition, the serum thioredoxin levels, an oxidative stress marker, to assess the antioxidant effect of edaravone was determined. In all cases, successful reperfusion was obtained within 6h after the onset of symptoms. Infarct size and reperfusion arrhythmia were significantly attenuated in the edaravone group compared with the placebo group (p=0.035 and p=0.031). The cumulative event-free rate was significantly higher in the edaravone group than in the placebo group (p=0.045). Serum thioredoxin levels were significantly lower in the edaravone group than in the placebo group throughout the acute phase. Conclusions: The present study suggests that the edaravone administration just prior to reperfusion might reduce oxidative stress and improve the long-term clinical outcomes of AMI patients.
DOI： 10.1253/circj.70.832
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Hayasaki T., Kaikita K., Okuma T., Yamamoto E., Kuziel W.A., Ogawa H., Takeya M.
Circulation Journal 70 ( 3 ) 342 - 351 2006年3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：Circulation Journal
Background: Monocyte chemoattractant protein-1 (MCP-1) and its major receptor, CC chemokine receptor 2 (CCR2), have been shown to contribute to left ventricular remodeling after myocardial infarction. However, it is unknown whether CCR2 deficiency protects the myocardium after myocardial ischemia-reperfusion. The purpose of the present study was to investigate the effects of CCR2 deficiency on myocardial ischemia-reperfusion injury in mice. Methods and Results: Experiments were performed in CCR2 and wild-type mice subjected to 45 min of ischemia followed by reperfusion. Macrophage infiltration in ischemic lesions was markedly reduced in CCR2 mice compared with wild-type mice (p<0.01). The infarct size was significantly reduced in CCR2 mice compared with wild-type mice at 3 days after reperfusion (p<0.001). In situ zymography revealed augmented gelatinolytic activity at 3 days after reperfusion in wild-type mice, but significantly less activity in CCR2 mice. NADPH oxidase activity, the intensity of nitrotyrosine staining and expression of inducible nitric oxide synthase and thioredoxin-1 were significantly increased in ischemic myocardium in wild-type mice compared with CCR2 mice, indicating a role for CCR2 in oxidative stress after ischemia-reperfusion. Conclusions: Inhibition of the MCP-1/CCR2 pathway may be a useful strategy for attenuating myocardial ischemia-reperfusion injury. -/- -/- -/- -/- -/-
DOI： 10.1253/circj.70.342
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Floating coronary artery thrombus prior to the onset of acute myocardial infarction 査読あり
Maruyoshi H., Sugiyama S., Araki S., Kojima S., Hayasaki T., Kaikita K., Fukushima S., Kageshita T., Sakamoto T., Yoshimura M., Ono T., Ogawa H.
Internal Medicine 45 ( 3 ) 173 - 174 2006年3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
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Hypoadiponectinemia is associated with coronary artery spasm in men 査読あり
Maruyoshi H., Kojima S., Otsuka F., Funahashi T., Kaikita K., Sugiyama S., Sakamoto T., Yoshimura M., Shimomura I., Ogawa H.
Circulation Journal 69 ( 9 ) 1154 - 1156 2005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：Circulation Journal
Background: The relationship between adiponectin and coronary spastic angina (CSA), both of which are closely involved in coronary endothelial dysfunction, has not been elucidated. Methods and Results: Plasma adiponectin concentrations were examined in 55 men with CSA and 55 with chest pain syndrome (CPS). The plasma log-adiponectin levels were significantly lower in patients with CSA than with CPS (0.61±0.28 vs 0.80±0.21• g•/ml, p<0.0001). The prevalence of smoking was significantly higher in the CSA patients than in those with CPS (50.9% vs 29.1%, p=0.0195). In multiple logistic regression analysis, log-adiponectin (p=0.0008) and smoking (p=0.0210) were independent determinants of CSA. Conclusions: Hypoadiponectinemia is a potential risk factor for CSA in men, independent of smoking.
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Komohara Y., Terasaki Y., Kaikita K., Suzuki H., Kodama T., Takeya M.
Developmental Dynamics 232 ( 1 ) 67 - 74 2005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：Developmental Dynamics
Elimination of apoptotic cells is an important mechanism to maintain proper embryonal morphogenesis. The class A scavenger receptor type I, II (CD204), one of the major receptors expressed on macrophages, is a receptor actively involved in recognition and ingestion of apoptotic cells. To clarify the role of CD204 in embryonic morphogenesis, we performed immunohistochemical and immunoelectron microscopic studies using CD204-deficient mouse embryos. In control mice, almost all macrophages expressed CD204 from embryonic day 9.5 (E9.5). Phagocytes engulfing dead cells in the E13.5 interdigit region showed strong expression of CD204, indicating that CD204 was actively involved in apoptotic cell clearance. However, CD204 is not essential for the embryonic clearance of apoptotic cells, because CD204-deficient embryos developed normally without any retardation in footplate remodeling. Up-regulation of CD36 in CD204-deficient fetal macrophages suggested that CD36 substitutes for CD204 function. We also found that mesenchymal cells frequently engulfed apoptotic cells especially in early embryonal stages. These data suggest that CD204 is partially but not essentially involved in apoptotic cell clearance in embryogenesis. During early embryonal development, mesenchymal cells, rather than macrophages, play a major role in apoptotic cell clearance. © 2004 Wiley-Liss, Inc.
DOI： 10.1002/dvdy.20206
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Okuma T., Terasaki Y., Kaikita K., Kobayashi H., Kuziel W.A., Kawasuji M., Takeya M.
Journal of Pathology 204 ( 5 ) 594 - 604 2004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：Journal of Pathology
Macrophage infiltration is implicated in various types of pulmonary fibrosis. One important pathogenetic process associated with pulmonary fibrosis is injury to basement membranes by matrix metalloproteinases (MMPs) that are produced mainly by macrophages. In this study, C-C chemokine receptor 2-deficient (CCR2-/-) mice were used to explore the relationship between macrophage infiltration and MMP activity in the pathogenesis of pulmonary fibrosis, using the bleomycin-induced model of this disease process. CCR2 is the main (if not only) receptor for monocyte chemoattractant protein-1/C-C chemokine ligand 2 (MCP-1/CCL2), which is a critical mediator of macrophage trafficking, and CCR2-/-mice demonstrate defective macrophage migration. Pulmonary fibrosis was induced in CCR2-/- and wild-type (CCR2+/+) mice by intratracheal instillation of bleomycin. No significant differences in the total protein concentration in bronchoalveolar lavage (BAL) fluid, or in the degree of histological lung inflammation, were observed in the two groups until day 7. Between days 3 and 21, however, BAL fluid from CCR2-/- mice contained fewer macrophages than BAL fluid from CCR2+/+ mice. Gelatin zymography of BAL fluid and in situ zymography revealed reduced gelatinolytic activity in CCR2-/-mice. Immunocytochemical staining showed weaker expression of MMP-2 and MMP-9 in macrophages in BAL fluid from CCR2-/- mice at day 3. Gelatin zymography of protein extracted from alveolar macrophages showed reduced gelatinolytic activity of MMP-2 and MMP-9 in CCR2-/- mice. At days 14 and 21, lung remodelling and the hydroxyproline content of lung tissues were significantly reduced in CCR2-/- mice. These results suggest that the CCL2/CCR2 functional pathway is involved in the pathogenesis of bleomycin-induced pulmonary fibrosis and that CCR2 deficiency may improve the outcome of this disease by regulating macrophage infiltration and macrophage-derived MMP-2 and MMP-9 production. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
DOI： 10.1002/path.1667
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Kaikita K., Hayasaki T., Okuma T., Kuziel W.A., Ogawa H., Takeya M.
American Journal of Pathology 165 ( 2 ) 439 - 447 2004年8月
担当区分：筆頭著者, 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 Pathology
A key component of cardiac remodeling after acute myocardial infarction (MI) is the inflammatory response, which modulates cardiac tissue repair. The purpose of this study was to investigate the relationship between the monocytic inflammatory response and left ventricular remodeling after MI using mice deficient in CC chemokine receptor 2 (CCR2), the primary receptor for the critical regulator of CC chemokine ligand 2. Immunohistochemical analysis revealed rapid infiltration of macrophages into infarcted tissue within 7 days in wild-type (WT) mice. However, this process was greatly impaired in CCR2-deficient (CCR2 ) mice. Echocardiography demonstrated beneficial effects of CCR2 deficiency on left ventricular remodeling at 7 and 28 days after MI. In situ zymography showed augmented gelatinolytic activity in WT mice within 7 days after MI, whereas gelatinolytic activity was barely detectable in CCR2 mice. Moreover, the distribution of gelatinolytic activity in serial sections was very similar to the distribution of macrophages rather than neutrophils. Expression of matrix metalloproteinases and tumor necrosis factor-α mRNAs was up-regulated in infarcted regions from WT mice compared to CCR2 mice at 3 days after MI. Direct inhibition of CCR2 functional pathway might contribute to the attenuation of left ventricular remodeling after MI. -/- -/- -/-
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Effects of Nicorandil on Endogenous Fibrinolytic Capacity in Patients with Coronary Artery Disease 査読あり
Sakamoto T., Kaikita K., Miyamoto S., Kojima S., Sugiyama S., Yoshimura M., Ogawa H.
Circulation Journal 68 ( 3 ) 232 - 235 2004年3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：Circulation Journal
Background: Nicorandil is a hybrid-type anti-anginal drug that combines a KATP channel opener and a nitric oxide donor. Recently the IONA study reported that nicorandil improves the prognosis of patients with stable angina pectoris. Methods and Results: To examine the effects of nicorandil on endogenous fibrinolysis, plasma concentrations of tissue-type plasminogen activator (t-PA) antigen, type-1 plasminogen activator inhibitor (PAI-1) antigen and PAI activity were measured in consecutive 11 patients (7 men and 4 women, mean age 63 years, ranges 41-84 years) with coronary artery disease. Nicorandil (15 mg/day) was administered orally to each patient for 2 weeks. Venous blood samples were obtained from each patient before and after the administration of the drug in the early morning before eating. There were no significant changes in the plasma concentrations of t-PA (12.4±1.9 to 9.8±1.5) or PAI-1 (26.3±3.9 to 21.5±4.9) antigens (ng/ml, mean±SEM) before and after nicorandil administration. On the other hand, the plasma activity of PAI (IU/ml, mean±SEM) decreased significantly after the treatment (12.9±3.2 to 5.6±1.9, p=0.039). Conclusions: It is well known that PAI activity determines the whole fibrinolytic capacity and oral administration of nicorandil decreased PAI activity in patients with coronary artery disease. This finding suggests that nicorandil improves the fibrinolytic capacity and may reduce the risk of coronary thrombus formation in such patients.
DOI： 10.1253/circj.68.232
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Suzuki S., Sugiyama S., Usuku H., Hirai N., Kaikita K., Sakashita N., Sakamoto T., Yoshimura M., Ogawa H.
Internal Medicine 43 ( 3 ) 199 - 203 2004年3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
We report a 67-year-old Japanese man who presented with worsening heart failure with asymptomatically transient ischemic ST-segment depression. Left ventriculography showed diffuse hypokinesis; asymptomatic coronary artery spasm was evoked by the acetylcholine provocation test. Endomyocardial biopsy exhibited hypertrophic cardiomyocytes and scattered microscopic focal myocardial necrosis with amyloid-deposition. Transient ST-segment depression improved after treatment with a calcium antagonist, but cardiac contraction was still impaired. We hypothesize that asymptomatic coronary spasm may cause irreversible cardiac damage and heart failure with amyloid-deposition; the presence or absence of coronary spasm in heart failure patients should be clarified in order to determine therapeutic strategy.
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Kaikita K., Schoenhard J.A., Painter C.A., Ripley R.T., Brown N.J., Fogo A.B., Vaughan D.E.
Journal of Molecular and Cellular Cardiology 34 ( 6 ) 617 - 627 2002年6月
担当区分：筆頭著者 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
Recent studies have indicated that a number of factors contribute to the pathophysiology in response to nitric oxide synthase (NOS) inhibition. We previously demonstrated that plasminogen activator inhibitor-1 deficient (PAI-1 ) mice are protected against hypertension and perivascular fibrosis induced by relatively short-term NOS inhibition. In this study, we compared the temporal changes in systolic blood pressure and coronary perivascular fibrosis induced by long-term treatment with N -nitro-L-arginine methyl ester (L-NAME) in wild type (WT), PAI-1 and tissue-type plasminogen activator deficient (t-PA ) mice. After initiating L-NAME, systolic blood pressure increased in all groups at 2 weeks. Over a 16 week study period, systolic blood pressure increased to 143±3 mmHg (mean±SEM) in WT animals, 139±2 in t-PA mice vs 129±2 in PAI-1 mice (P < 0.01). Coronary perivascular fibrosis increased in L-NAME-treated WT and t-PA mice compared to each control group (P < 0.01 in WT, P < 0.05 in t-PA ), while PAI-1 mice were protected against fibrosis induced by L-NAME. t-PA deficiency did not accentuate the vascular pathology or the changes in blood pressure. In situ zymography demonstrated augmented gelatinolytic activity in PAI-1 mice at baseline, suggesting that PAI-1 deficiency prevents the increase of collagen deposition by promoting matrix degradation. Plasma TGF-β1 levels increased in L-NAME-treated WT and PAI-1 mice (P < 0.01), but not in L-NAME-treated t-PA mice. These findings support the hypothesis that the plasminogen activator system protects against the structural vascular changes induced by long-term NOS inhibition. While PAI-1 deficiency protects against L-NAME-induced hypertension and perivascular fibrosis, t-PA deficiency does not exacerbate the vascular pathology or hypertension. © 2002 Elsevier Science Ltd. All rights reserved. -/- ω -/- -/- -/- -/- -/- -/- -/- -/- -/- -/-
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Kaikita K., Fogo A., Ma L., Schoenhard J., Brown N., Vaughan D.
Circulation 104 ( 7 ) 839 - 844 2001年8月
担当区分：筆頭著者 記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Circulation
Background - Long-term inhibition of nitric oxide synthase (NOS) is known to induce hypertension and perivascular fibrosis. Recent evidence also suggests that long-term NOS inhibition induces expression of plasminogen activator inhibitor-1 (PAI-1) in vascular tissues and that PAI-1 may contribute to the development of fibrosis after chemical or ionizing injury. On the basis of these observations, we hypothesized that PAI-1 may influence the vascular response to long-term NOS inhibition by N -nitro-L-arginine methyl ester (L-NAME). Methods and Results - We compared the temporal changes in systolic blood pressure and coronary perivascular fibrosis in PAI-1-deficient (PAI-1 ) and wild-type (WT) male mice (N=6 per group). At baseline, there were no significant differences in blood pressure between groups. After initiation of L-NAME, systolic blood pressure increased in both groups at 2 weeks. Over an 8-week study period, systolic blood pressure increased to 141 ± 3 mm Hg in WT animals versus 112 ± 4 mm Hg in PAI-1 mice (P<0.0001). The extent of coronary perivascular fibrosis increased significantly in L-NAME-treated WT mice (P<0.01 versus PAI-1 mice). Cardiac type I collagen mRNA expression was greater in control (P<0.01) and L-NAME-treated PAI-1 (P<0.05) groups than in control WT mice, indicating that PAI-1 deficiency prevents the increase of collagen deposition by promoting matrix degradation. Conclusions - These findings suggest that PAI-1 deficiency alone is sufficient to protect against the structural vascular changes that accompany hypertension in the setting of long-term NOS inhibition. Direct inhibition of vascular PAI-1 activity may provide a new therapeutic strategy for the prevention of arteriosclerotic cardiovascular disease. ω -/- -/- -/- -/-
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Soejima H., Ogawa H., Suefuji H., Kaikita K., Takazoe K., Miyamoto S., Kajiwara I., Shimomura H., Sakamoto T., Yoshimura M., Nakamura S.
American Journal of Cardiology 87 ( 12 ) 1408 - 1411 2001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：American Journal of Cardiology
In conclusion, this study demonstrates that losartan and enalapril improved hypercoagulability in patients with AMI associated with improvement in impaired fibrinolysis.
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Ogawa H., Sakamoto T., Nishiyama K., Soejima H., Kaikita K., Takazoe K., Miyamoto S., Kugiyama K., Yoshimura M., Yasue H.
Japanese Circulation Journal 64 ( 3 ) 170 - 176 2000年3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：Japanese Circulation Journal
The cell surface expression of intercellular adhesion molecule-1 (ICAM- 1) is upregulated following activation during inflammatory responses, mediating both cell migration and activation. The involvement of inflammation in unstable angina is suggested by the presence of activated circulating leukocytes. To examine whether plasma soluble ICAM-1 (sICAM-1) levels increase in the coronary circulation of patients with coronary organic stenosis and coronary spasm, plasma sICAM-1 levels were measured in the coronary sinus (CS) and the aortic root (Ao) simultaneously in 10 patients with 90% or more coronary narrowing and coronary spasm (coronary spastic angina (CSA) with organic stenosis), in 11 patients with coronary spasm and no significant coronary narrowing (CSA without organic stenosis), in 16 patients with stable exertional angina, and in 13 control subjects. The plasma sICAM-1 levels (ng/ml) in the CS increased in CSA with organic stenosis (230±26) as compared with CSA without organic stenosis (158±14), stable exertional angina (130±9) and control subjects (121±10) (p<0.01). The levels in the Ao also increased in CSA with organic stenosis (208±24) as compared with CSA without organic stenosis (149±13), stable exertional angina (130±11) and control subjects (121±10) (p<0.01). Furthermore, the plasma sICAM-1 levels were higher in the CS than in the Ao only in CSA with organic sterosis. These results suggest that activation of leukocytes occurs through the induction of ICAM-1 in the coronary circulation in the patients with CSA with organic stenosis.
DOI： 10.1253/jcj.64.170
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Difference in fibrinolytic activity between multivessel coronary spasm and one-vessel coronary spasm 査読あり
Ogawa H., Suefuji H., Takazoe K., Soejima H., Sakamoto T., Miyamoto S., Kaikita K., Yoshimura M., Kugiyama K., Yasue H.
American Journal of Cardiology 85 ( 1 ) 98 - 101 2000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：American Journal of Cardiology