2007年3月15日
●SY-01 シンポジウム 01
冠動脈疾患の New Evidence - 病態， 診断， 治療
3月15日(木) 08:30-10:00
第1会場（ポートピアホール）
『Establishment of Pentraxin 3(PTX3) ELISA System for the Evaluation of Acute Coronary Syndrome』
井上 健司 先生 （順天堂大学附属練馬病院 循環器内科）
Kenji Inoue*1, Shinya Okazaki*1, Yasunobu Kawano*1 ,Kaoru Komatsu*1, Sonomi Maruyama*1, Iwao Okai*1, Yasumasa Fujiwara*1, Takeshi Kurata*2, Katsumi Miyauchi*2, Tatsuhiko Kodama*3, Hiroyuki Daida*2,
Department of Cardiology, Juntendo Nerima Hospital*1, Juntendo University*2, University of Tokyo, RCAST*3
Patients with acute coronary syndromes (ACS) span a large spectrum of risk that progresses from unstable angina (UA) to acute myocardial infarction (AMI). Biomarkers are being used as tools to identify patients with ACS. We identified pentraxin 3 (PTX3) as being suppressed by statin treatment mostly in human umbilical vein endothelial cells (EC) by cDNA microarray. PTX3 belongs same family with CRP, and is also made in response to primary proinflammatory signals by diverse cell types, predominantly macrophages and vascular EC, but not liver, unlike CRP. To evaluate the role of PTX3 in ACS, a sensitive and precise measurement of PTX3 concentration is needed. We established a high sensitive plasma ELISA assay system for the detection of PTX3 using monoclonal antibodies. The sensitivity was far greater than the current commercially available kit. Plasma samples were obtained from 162 consecutive patients treated for hypertension, hyperlipidemia, diabetes mellitus, or cardiovascular disease at a physician's office. PTX3 was not associated with any coronary risk factors. Additionally, we collected plasma samples from 252 consecutive subjects admitted to a hospital for coronary artery assessment by coronary angiography. PTX3 was significantly increased in patients in whom coronary intervention was performed. We further analyzed the plasma level of PTX3 in 24 patients with UA. Compared to the control group, PTX3 were three times higher in the UA group. Furthermore, Top 3 highest values of PTX3 (all were patients with AMI) showed extremely poor clinical outcome. From these results, PTX3 was an ideal vascular inflammation marker, and can diagnose of UA and may predict an outcome of AMI.
Additional Remarks
『Long Pentraxin PTX3 as a Novel Marker for Stent-induced Inflammation and Coronary Restenosis』
琴岡 憲彦 先生 （佐賀大学 循環器内科）
Norihiko Kotooka*1, Teruo Inoue*1, Koichi Node*1,
Department of Cardiovascular and Renal Medicine, Saga University Faculty of Medicine*1
Inflammation in the vessel wall plays an essential role in the process of atherogenesis, plaque vulnerability, and restenosis after percutaneous coronary intervention. Unlike classic short pentraxin CRP is produced mainly by the liver, prototypic member of the long-pentraxin family pentraxin3 (PTX3) is synthesized at the inflammatory site by vascular endothelial cells, smooth muscle cells, monocytes/macrophages and neutrophiles in response to primary inflammatory stimuli, including oxidized LDLs. It has been described that PTX3 is present in advanced atherosclerotic lesions and its plasma concentration is increased in acute myocardial infarction or vasculitis, therefore it is called "vessel-related pentraxin". We demonstrated that plasma PTX3 levels as well as high-sensitivity (hs)-CRP and activated Mac-1 on the surface of neutrophils were elevated after coronary stent implantation in 20 patients undergoing elective percutaneous coronary intervention (PCI), and transcardiac PTX3 gradient (0.40±0.64 V.S. -0.19±0.33 ng/ml, P=0.02) 15 min after PCI and relative increase in PTX3 (350±180 V.S. 151±91 %, P=0.01) 24hrs after PCI in coronary sinus was significantly higher in 6 patients who experienced restenosis than in remaining 14 who did not, and later was correlated with that in hs-CRP (R=0.65, P<0.01) and activated Mac-1 (R=0.52, P<0.05) at 48 hrs. Multiple regression analysis that included variables obtained from quantitative coronary angiography and peripheral blood sample demonstrated that relative increase in PTX3 at 48 hrs was the most powerful predictor of late lumen loss (standard regression coefficient 0.547, P<0.01).So we concluded that coronary stenting enhanced circulating PTX3 levels in association with an inflammatory response. PTX3 may be a useful marker for evaluation of stent-induced inflammatory reaction.
●FRS02 Featured Research Session 02
Pathophysiology of Cardiovascular Disease
3月15日(木) 16:20-18:00
第4会場（神戸ポートピアホテル南館 1F 大輪田C）
FRS-033
『Pentraxin 3, a New Marker for Vascular Inflammation, Predicts Adverse Clinical Outcomes in Patients with Heart Failure』
鈴木 聡 先生 （山形大学 循環・呼吸・腎臓内科学）
Satoshi Suzuki*1, Yasuchika Takeishi*1, Takeshi Niizeki*1, Toshiki Sasaki*1, Yo Koyama*1, Tatsuro Kitahara*1, Naoki Nozaki*1, Osamu Hirono*1, Tetsu Watanabe*1, Joji Nitobe*1, Yuichi Tsunoda*1, Mutsuo Harada*1, Isao Kubota*1,
Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine*1
Background: Pentraxin 3 (PTX3) is a member of the pentraxin superfamily. The classical short pentraxin, C-reactive protein, is produced in the liver in response to inflammatory signals. PTX3, one of the long pentraxin, is rapidly produced and released from macrophages, endothelial cells and smooth muscle cells in response to primary inflammatory signals. The purpose of this study was to examine clinical significance of plasma PTX3 levels in patients with congestive heart failure (CHF). Methods: Plasma PTX3 levels were measured in 148 patients who were hospitalized for CHF and 25 control subjects without CHF. They were followed-up for 548 ± 321 days with the end points of cardiac death and re-hospitalization due to progressive heart failure. Results: Plasma PTX3 levels increased with advancing New York Heart Association (NYHA) functional class (NYHA I: 3.3 ± 2.2, II: 4.4 ± 2.9, III: 11.1 ± 22.9, IV: 26.3 ± 33.7 ng/ml, P < 0.0001). The plasma PTX3 level was higher in cardiac event group than in event free group (15.8 ± 30.3 vs. 5.5 ± 5.7 ng/ml, P=0.0014). Kaplan-Meier survival curves demonstrated that cardiac event rate was markedly higher in high PTX3 group than in normal PTX3 group (51.3% vs. 21.3%, P=0.0008). Conclusion: Plasma PTX3 level predicts adverse clinical outcomes in patients with CHF.
●OE08 Oral Presentation (English) 08
Atherosclerosis, clinical-01
3月15日(木) 11:10-12:40
第13会場（神戸ポートピアホテル本館 B1F 布引＋北野
OE-044
『Long Pentraxin 3 (PTX3) is More Specific than C-reactive Protein (CRP) as a Marker for Vascular Inflammation』
志賀 太郎 先生 （東京大学 循環器内科学）
Taro Shiga*1, Koji Maemura*1, Yasushi Imai*1, Norihiko Takeda*1, Jiro Ando*1, Toshihiro Morita*1, Ichiro Manabe*1, Doubun Hayashi*1, Akira Sugiyama*3, Yasunobu Hirata*1, Tatsuhiko Kodama*2, Ryozo Nagai*1,
Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo*1, Laboratory for Systems Biology and Medicine, Research Center for Advanced Science and Technology, The University of Tokyo*2, Perseus Proteomics Inc.*3
The long pentraxin 3 (PTX3) is one of inflammation markers that shares structural homology with C-reactive protein (CRP), and is produced abundantly from atherosclerotic lesion while CRP is mainly produced in the liver. Thus PTX3 is expected to be a more specific marker for cardiovascular inflammation. We first confirmed PTX3 but not CRP from cultured human endothelial cells, while CRP was induced in cultured hepatocytes by IL-6. Then we examined PTX3 and CRP levels in 269 consecutive patients (20 to 89 years old age, 74 % male). There was no significant correlation between PTX3 and CRP levels (Spearman's ρ=0.158). Notably, PTX3 levels in patients taking statins or aspirin were lower than non-taking patients. Among all enrolled patients, PTX3 but not CRP levels were significantly higher in the acute coronary syndrome (ACS) group than other groups. Only after exclusion of patients with intercurrent diseases that may affect CRP levels, both PTX3 and CRP levels were higher in unstable angina (UAP) group than stable angina group. However, the ROC analysis showed PTX3 was superior to CRP for the detection of UAP. Finally neither PTX3 nor CRP showed any apparent correlation with the number of diseased vessels. PTX3 levels were elevated in UAP patients. PTX3 may reflect active inflammation that leads to plaque rupture more specifically than CRP.
●OJ14 一般口述 （日本語） 14
Coronary revascularization, PCI-05
3月15日(木) 16:30-18:00
第8会場（神戸ポートピアホテル南館 B1F ルビー）
OJ-078
『Reciprocal Changes in Plasma Pentraxin 3 and C-reactive Protein after Percutaneous Coronary Intervention in Patients with Stable Angina』
井手口 武史 先生 （宮崎大学 第一内科）
Takeshi Ideguchi*1, Takuroh Imamura*1, Haruhiko Date*1, Shohei Koyama*1, Makoto Tatsumoto*1, Junji Kawagoe*1, Yasuko Nagoshi*1, Hisamitsu Onitsuka*1, Katsuhiro Nozaki*1, Hironao Iwakiri*1, Kazuo Kitamura*1, Tatsuhiko Kodama*2,
First Department of Internal Medicine, University of Miyazaki*1
Systems Biology and Medicine, Research Center for Advanced Science and Technology, The University of Tokyo*2
Background: Pentraxin 3 (PTX3) and C-reactive protein (CRP) belong to the pentraxin protein family and these expressions are induced in response to inflammatory stimuli. PTX3 is produced by macrophages, endothelial cells and smooth muscle cells in the atherosclerotic plaque, but is not produced by hepatocytes, which are a major source of CRP. Therefore, PTX3 might be a more specific marker of the atherosclerosis. We investigated whether the plaque rupture or arterial wall injury caused by percutaneous coronary intervention (PCI) affects the plasma levels of PTX3 and CRP in the local coronary circulation.Methods: We examined 25 patients with stable angina undergone PCI for the proximal lesion of the left anterior descending coronary artery (LAD). Plasma concentrations of PTX3 and CRP at the great cardiac vein (GCV) which selectively drains blood from the LAD were measured before and after PCI. Results: The plasma levels of PTX3 at GCV were significantly increased after PCI (mean; 4.71 vs. 5.87 ng/mL, p<0.001), in contrast those of CRP at GCV were significantly decreased after PCI (mean; 2.30 vs 2.17 mg/L, p<0.001). Conclusion: PTX3 might be released from the ruptured plaque or injured arterial wall after PCI, indicating local production in the plaque, whereas CRP could be taken up in the ruptured plaque after PCI, suggesting systemic production in the liver.
●PJ025 ポスターセッション （日本語） 025
Acute coronary syndrome, basic /clinical-7
3月15日(木) 15:30-16:15
第25会場（神戸国際展示場 1号館 2F 展示室）
PJ-142
『Release of the Long Pentraxin PTX3 in Vulnerable Plaques in vivo』
岡井 巌 先生 （順天堂練馬病院 循環器内科）
●PJ032 ポスターセッション （日本語） 032
Angina pectoris, basic / clinical-4
3月15日(木) 15:30-16:15
第25会場（神戸国際展示場 1号館 2F 展示室）
PJ-187
『Pentraxin 3, a New Marker for Vascular Inflammation, is Increased in Patients with Unstable Angina Pectoris』
佐々木 敏樹 先生 （山形大学 循環・呼吸・腎臓内科学）
2007年3月16日
●ACC-JCSジョイントシンポジウム
「Detection and Treatment of Vulnerable Patients」
3月16日(金) 13:50-15:20
第16会場（神戸国際会議場 3F 国際会議室）
『Management of Vulnable Plaque and Vulnable Patients』
野出 孝一 先生 （佐賀大学 循環器内科）
●PE040 Poster Session (English) 040
Heart failure, clinical-07
3月16日(金) 10:10-10:55
第25会場（神戸国際展示場 1号館 2F 展示室）
PE-235
『Prognostic Value of Long Pentraxin3 in Patients with Congestive Heart Failure』
琴岡 憲彦 先生 （佐賀大学 循環器内科）
●PJ072 ポスターセッション （日本語） 072
Atherosclerosis, clinical-12
3月16日(金) 15:30-16:15
第25会場（神戸国際展示場 1号館 2F 展示室）
PJ-426
『Pentraxin 3 is a Causative ''Maker'' Rather than a Surrogate ''Marker'' of Stable Coronary Plaque』
井手口 武史 先生（宮崎大学 第一内科）
●PJ076 ポスターセッション （日本語） 076
Coronary circulation, basic / clinical-2
3月16日(金) 15:30-16:15
第25会場（神戸国際展示場 1号館 2F 展示室）
PJ-454
『Epicardial Adipose Tissue Contains C-Reactive Protein and Pentraxin 3 Which may be Released into Coronary Circulation』
今村 卓郎 先生 （宮崎大学 第一内科） |
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