Papers - KAIKITA Koichi
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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 2008.11
Publishing type：Research paper (scientific journal)
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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 2008.7
Language：English Publishing type：Research paper (scientific journal) Publisher：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 2008.6
Language：English Publishing type：Research paper (scientific journal) Publisher：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 2008.5
Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：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 2008.4
Publishing type：Research paper (scientific journal)
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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 2008.2
Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：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 2007.12
Language：English Publishing type：Research paper (scientific journal) Publisher：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 2007.12
Authorship：Lead author Publishing type：Research paper (scientific journal)
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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 2007.11
Language：English Publishing type：Research paper (scientific journal) Publisher：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 2007.9
Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：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.
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Honda T., Sugiyama S., Sakamoto T., Kaikita K., Ogawa H.
Circulation Journal 71 ( 8 ) 1263 - 1267 2007.8
Language：English Publishing type：Research paper (scientific journal) Publisher：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 2007.8
Language：English Publishing type：Research paper (scientific journal) Publisher：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 2007.4
Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：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 2006.12
Language：English Publishing type：Research paper (scientific journal) Publisher：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 2006.12
Language：English Publishing type：Research paper (scientific journal) Publisher：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 Reviewed
Kaikita K＊, Soejima K, Matsukawa M, Nakagaki T, Ogawa H
J Thromb Haemost 4 ( 11 ) 2490 - 2493 2006.8
Authorship：Lead author, Corresponding author Language：English Publishing type：Research paper (scientific journal)
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Long-term efficacy of edaravone in patients with acute myocardial infarction Reviewed
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 2006.7
Language：English Publishing type：Research paper (scientific journal) Publisher：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 2006.3
Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：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 Reviewed
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 2006.3
Language：English Publishing type：Research paper (scientific journal) Publisher：Internal Medicine
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Hypoadiponectinemia is associated with coronary artery spasm in men Reviewed
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 2005.9
Language：English Publishing type：Research paper (scientific journal) Publisher：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.