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医学部 医学科 内科学講座循環器・腎臓内科学分野 |
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准教授 |
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Inflammatory stimuli and hypoxia on atherosclerotic plaque thrombogenicity: Linking macrophage tissue factor and glycolysis 査読あり
Kazunari Maekawa, Eriko Nakamura, Yoichi Saito, Yunosuke Matsuura, Toshihiro Gi, Kensaku Nishihira, Nobuyuki Oguri, Sayaka Moriguchi-Goto, Yuichiro Sato, Kinta Hatakeyama, Yoshisato Shibata, Yoshihiro Komohara, Koichi Kaikita, Yujiro Asada, Atsushi Yamashita
PLoS ONE 20 ( 3 March ) 2025年3月
記述言語：英語 掲載種別：研究論文（学術雑誌）
Background The thrombogenic potential of cells within atherosclerotic plaques is critical in the formation of a coronary thrombus. We hypothesized that a combination of inflammatory and hypoxic stimuli enhances tissue factor (TF) expression and glycolysis in cells in atherosclerotic plaques and contributes to coronary thrombus formation. Aims To identify TF- and hexokinase (HK)-II-expressing cells in coronary atherosclerotic plaques and thrombi and determine the effects of combined inflammatory and hypoxic stimuli and glycolysis on TF expression in peripheral blood mononuclear cell-derived macrophages. Methods We immunohistochemically assessed TF and HK-II expression in stable (n = 20) and unstable (n = 24) human coronary plaques and aspirated acute coronary thrombi (n = 15). The macrophages were stimulated with tumor necrosis factor-α, interferon-γ, or interleukin-10 under normoxic (21% O2) or hypoxic (1% O2) conditions, and TF expression was assessed. Results TF and HK-II expression were increased in unstable plaques compared with stable plaques. The number of CD68- and HK-II-immunopositive cells positively correlated with the number of TF-immunopositive cells. TF- and HK-II-expressing macrophages, which expressed M1- or M2-like markers, were involved in platelet-fibrin thrombus formation in ruptured plaques. The combination of inflammatory and hypoxic conditions additively augmented TF expression and procoagulant activity in the cultured macrophages. Inhibition of glycolysis with 2-deoxyglucose reduced the augmented TF expression and procoagulant activity. Conclusion Combined inflammatory and hypoxic conditions in atherosclerotic plaques may markedly enhance procoagulant activity in macrophages and contribute to coronary thrombus formation following plaque disruption. Macrophage TF expression may be associated with glycolysis.
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A case of rapidly progressive Salmonella aortic aneurysm with acute pericarditis manifesting as a precursor 査読あり
Koshiro Harada, Katsuya Kawagoe, Yunosuke Matsuura, Mana Kawano, Yosuke Suiko, Hiroki Tanaka, Kohei Moribayashi, Hirohito Ishii, Takeshi Ideguchi, Koji Furukawa, Koichi Kaikita
Journal of Cardiology Cases 31 ( 3 ) 76 - 79 2025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）
We report a case of Salmonella cardiovascular infection presenting with acute pericarditis as a precursor to the rapid progression of aortic aneurysm. An 81-year-old man presented with persistent fever and chest pain worsened with inspiration and was admitted to a nearby hospital with a diagnosis of bacterial pericarditis. However, hoarseness emerged two days later, and the patient was transferred to our hospital because of concerns about extracardiac inflammatory foci. Computed tomography (CT) revealed a periaortic exudate and aortic arch aneurysm. After transfer, blood cultures confirmed Salmonella infection. Ampicillin (ABPC) was initiated for long-term treatment of Salmonella infection, and pericarditis was treated with ibuprofen and colchicine for approximately one month. The associated symptoms and inflammatory blood data significantly improved, but five weeks later, follow-up CT revealed enlargement of the arch aneurysm. Due to the patient's age and nutritional status, thoracic endovascular aortic repair (TEVAR) was performed along with continued ABPC. Postoperatively, the infection was well-controlled, and follow-up CT revealed a size reduction in the treated aneurysm. No recurrent Salmonella-related vascular events were observed for two years after TEVAR. Learning objective: Acute pericarditis can present as a precursor to life-threatening vascular lesions associated with Salmonella infection and requires timely and appropriate diagnosis of the etiology behind the manifestation. Patients with aortic aneurysms caused by Salmonella often do not tolerate invasive surgical treatment when diagnosed, and the lesions progress rapidly. Therefore, endovascular treatment combined with long-term antibiotic therapy may be a practical option.
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宮崎県における心不全患者への退院時理学療法サマリー記載項目統一化に向けた調査研究 査読あり
花田 智, 松浦 祐之介, 藤﨑 修兵, 長嶺 庸介, 小山 彰平, 岩切 弘直, 海北 幸一
心臓リハビリテーション 30 ( 3.4 ) 2024年12月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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Basal inferoseptal segment is highly susceptible to deformation in the clinical spectrum of transthyretin-derived amyloid cardiomyopathy. 査読あり 国際誌
Toshihiro Tsuruda, Hiroshi Nakada, Yoshimasa Yamamura, Yunosuke Matsuura, Miyuki Ogata, Miyo Tanaka, Yosuke Suiko, Soichi Komaki, Hiroki Tanaka, Kohei Moribayashi, Takeshi Ideguchi, Tamasa Terada, Tomomi Ota, Keisuke Yamamoto, Kensaku Nishihira, Yoshisato Shibata, Koichi Kaikita
European heart journal open 4 ( 5 ) oeae076 2024年9月
記述言語：英語 掲載種別：研究論文（学術雑誌）
AIMS: While the prevalence of transthyretin-derived amyloid cardiomyopathy (ATTR-CM) is on the rise, detailed understanding of its morphological and functional characteristics within the left ventricle (LV) across heart failure (HF) remains limited. METHODS AND RESULTS: Utilizing two-dimensional (2D) speckle-tracking echocardiography, we assessed longitudinal strain (LS) in 63 histology-confirmed ATTR-CM patients. Additionally, cardiac magnetic resonance (CMR) images measured native T1 and extracellular volume (ECV), compared with LS across 18 LV segments. Patients were categorized into three groups based on HF status: Group 1 (no HF symptoms), Group 2 (HF with preserved LV ejection fraction), and Group 3 (HF with reduced LV ejection fraction). LS analysis unveiled susceptibility to deformation in the basal inferoseptal segment, persisting even in asymptomatic cases. CMR demonstrated increasing native T1 deviation, particularly evident in segments distant from the inferoseptal region. Contrastingly, maximal ECV was consistently observed in the basal and mid-ventricular inferior-septum, even in asymptomatic individuals. Segmental LS decline correlated with ECV expansion but not with native T1 values. CONCLUSION: Our findings suggest that the inferoseptal segment is highly susceptible to amyloid infiltration, and 2D speckle-tracking echocardiography and CMR may serve as a valuable tool for its early detection.
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Rewiring of the dissected branch along the jailed balloon technique in provisional stenting for true coronary bifurcation lesions 査読あり
Shintaro Izumoto, Kazumasa Kurogi, Kohei Moribayashi, Soichi Komaki, Yunosuke Matsuura, Nobuyasu Yamamoto, Toshihiro Tsuruda, Koichi Kaikita
Cardiovascular Revascularization Medicine: Interesting Cases 2 100018 - 100018 2024年6月
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内科臨床誌 メディチーナ Vol.60 No.13 特集 : 一般医家のためのDOAC時代の心房細動診療
小牧聡一, 松浦祐之介, 海北幸一（ 担当： 分担執筆 , 範囲: 18. PCI後の抗血栓療法をどうする？）
医学書院 2023年12月
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Abstract 4141123: Utility of Comprehensive Profiling of Blood Amino Acid in the Identification and Clinical Characterization of High-Risk Populations for Developing Future Adverse Events in Patients with Cardiovascular Disease
Kohei Moribayashi, Yunosuke Matsuura, Kinuko Yamamoto, Hiroki Tanaka, Soichi Komaki, Masashi Yamaguchi, Takeshi Ideguchi, Toshihiro Tsuruda, Koichi Kaikita
Circulation 150 ( Suppl_1 ) 2024年11月
記述言語：英語 掲載種別：研究発表ペーパー・要旨（国際会議） 出版者・発行元：Ovid Technologies (Wolters Kluwer Health)
Background: The associations of specific blood amino acid (AA) metabolite levels with frailty and heart failure have been reported. However, the utility of comprehensive AA profiling in cardiovascular disease (CVD) patients remains unknown.
Aims: This study aimed to determine whether plasma AA profiling through hierarchical clustering analysis (HCA) can identify and clinically define a high-risk population prone to future adverse events.
Methods: We enrolled 267 patients (mean age 74 years, 60% male) with CVD (118 with ischemic heart disease, 85 with valvular heart disease, 33 with cardiomyopathy, and 31 with other CVD). In fasting plasma samples, 39 AA metabolite levels were measured using liquid chromatography-mass spectrometry. Hierarchical clustering was used for data analysis. Major adverse cardiovascular events (MACE) were defined as a composite of all-cause mortality, nonfatal myocardial infarction, ischemic stroke, and rehospitalization for worsening heart failure. During a one-year follow-up, MACE incidence was compared across HCA-based patient clusters using Kaplan-Meier (KM) curve analysis. The cluster with the worst prognosis was characterized clinically compared to other clusters.
Results: HCA enabled patients to be categorized into four clusters (Figure 1A). KM curves showed that Cluster 2 had a significantly worse prognosis than other clusters (log-rank test; p=0.0018) (Figure 1B). AA metabolism in Cluster 2 was characterized by the lowest values of total AA, non-essential AA (NEAA), essential AA (EAA), branched-chain AA (BCAA), BCAA/total AA ratio, and NEAA/EAA ratio. Compared to non-Cluster 2 patients, those in Cluster 2 were older (p=0.004), had lower body weight (p=0.02), a higher prevalence of chronic kidney disease (p<0.0001), higher levels of brain natriuretic peptide (p<0.0001) despite similar left ventricular ejection fraction, lower albumin levels (p=0.001), and more frailty indicators, such as muscle weakness (p=0.002), slower walking speed (p=0.0003), and lower scores on the Short Physical Performance Battery (p=0.002).
Conclusion: Comprehensive blood AA profiling can effectively identify high-risk CVD patient groups and provide relevant clinical characterization for prognosis. -
Abstract 4141578: Clinical Determinants and Prognostic Significance of Angiopoietin-like Protein 3 in Patients with Cardiovascular Disease
Hiroki Tanaka, Yunosuke Matsuura, Kohei Moribayashi, Kinuko Yamamoto, Soichi Komaki, Masashi Yamaguchi, Takeshi Ideguchi, Koichi Kaikita
Circulation 150 ( Suppl_1 ) 2024年11月
記述言語：英語 掲載種別：研究発表ペーパー・要旨（国際会議） 出版者・発行元：Ovid Technologies (Wolters Kluwer Health)
Background: Angiopoietin-like protein 3 (ANGPTL3) has garnered attention as a target for managing clinical lipid profiles. However, the determinants of blood ANGPTL3 levels and their prognostic significance in cardiovascular disease (CVD) remain unclear.
Aims: This study aimed to investigate the clinical determinants and prognostic significance of serum ANGPTL3 levels in patients with CVD.
Methods: A total of 311 patients with CVD (mean age 71 years, 61% male, mean body mass index 24 kg/m <sup>2</sup> , 42% diabetic, median estimated glomerular filtration rate (eGFR) 57 mL/min/1.73 m <sup>2</sup> , 152 patients with ischemic heart disease, 75 with valvular heart disease, 30 with cardiomyopathy, 54 with other CVD) were enrolled. Serum ANGPTL3 levels were measured using an enzyme-linked immunosorbent assay (R&D Systems) and analyzed for associations with clinical characteristics and the incidence of major adverse cardiovascular events (MACE), including all-cause mortality, non-fatal myocardial infarction, heart failure hospitalization, and ischemic stroke during a one-year follow-up.
Results: Serum ANGPTL3 levels were significantly higher in females than in males (92 [78-112] vs. 74 [56-94] ng/mL, p < 0.0001). These levels showed positive correlations with age and the levels of CRP and BNP, while negative correlations were observed with eGFR, total bilirubin (T-bil), alanine aminotransferase (ALT), albumin (Alb), hemoglobin (Hb), and platelet counts. No association was found with lipid profiles or specific CVD etiologies. Multivariate analysis identified gender, CRP, eGFR, ALT, and Hb levels as independent determinants of serum ANGPTL3 levels. During the follow-up period, 30 patients developed cardiovascular events, and receiver operating characteristic curve analysis identified a serum ANGPTL3 cutoff of 90.7 ng/mL for optimal event discrimination. Kaplan-Meier analysis showed a significantly higher incidence of MACE in patients with ANGPTL3 levels above the cutoff than those below (log-rank test, p = 0.0013). Multivariate Cox regression analysis identified elevated ANGPTL3 level as an independent determinant of MACE (hazard ratio: 1.01; 95% confidence interval: 1.00-1.02; p = 0.018).
Conclusions: In patients with CVD, serum ANGPTL3 levels, determined by gender, inflammation, liver and renal function, and anemia, can discriminate populations at high risk of developing future cardiovascular events. -
T Tsuruda, H Nakada, Y Yamamura, Y Matsuura, Y Suiko, S Komaki, H Tanaka, K Moribayashi, T Ideguchi, T Terada, T Ota, K Yamamoto, K Nishihira, Y Shibata, K Kaikita
European Heart Journal 45 ( Supplement_1 ) 2024年10月
記述言語：英語 掲載種別：研究発表ペーパー・要旨（国際会議） 出版者・発行元：Oxford University Press (OUP)
Abstract
Background
The prevalence of transthyretin-derived cardiomyopathy (ATTR-CM) is increasing; however, understanding the morphological and functional manifestations within the left ventricle (LV) across the spectrum of heart failure (HF) remain limited.
Purpose
This study aims to assess the longitudinal strain (LS) using 2D speckle-tracking echocardiography in ATTR-CM patients and compared them with the features of magnetic resonance imaging (MRI).
Methods
2D speckle-tracking echocardiography evaluated LS in 63 histology-confirmed ATTR-CM patients (median age: 78 years; male: 94%), with and without developing HF. Additionally, native T1 and extracellular volume (ECV) measured using MRI were compared with LS in 18-segments depicted on a Bull’s eye plot.
Results
Patients were grouped based on HF status: Group 1 (no HF symptoms, n=10), Group 2 (HF with preserved LV ejection fraction (LVEF), n=17), and Group 3 (reduced LVEF, n=36). Group 3 exhibited higher levels of brain natriuretic peptide and troponin T, and lower estimated glomerular filtration rate, compared with Group 1 and 2. Echocardiography revealed heightened LV thickness and decreased LVEF in Group 3. LS analysis revealed susceptibility to deformation in the basal inferior-septal segment, persisting even in Group 1. MRI revealed a high average native T1 level with minimal standard deviation (indicative of tissue homogeneity). However, this level increased as distance from the inferior-septal segment grew in the basal and mid-ventricular slices. Contrast images displayed maximal ECV in the basal and mid-ventricular inferior-septum, a phenomenon persisting in Group 1. Segmental LS decline, as assessed by echocardiography, correlated with ECV expansion but not with native T1 values.
Conclusion
2D speckle-tracking echocardiography can identify segmental LS impairment in ATTR-CM patients, potentially reflecting amyloid burden and fibrosis extent. Our data suggest that amyloid deposition might be widespread from the basal inferior-septal segment to other areas. -
Y Suiko, Y Matsuura, T Gi, H Tanaka, S Komaki, K Moribayashi, Y Yamamura, T Ideguchi, A Yamashita, T Tsuruda, K Kaikita
European Heart Journal 45 ( Supplement_1 ) 2024年10月
記述言語：英語 掲載種別：研究発表ペーパー・要旨（国際会議） 出版者・発行元：Oxford University Press (OUP)
Abstract
Background
The pathophysiology of coronary microvascular disease (CMD) in patients with transthyretin amyloidosis cardiomyopathy (ATTR-CM) remains unclear.
Objective
This study aims to functionally and pathologically assess coronary microvasculature to elucidate the underlying mechanisms of myocardial injury in patients with ATTR-CM.
Methods
Fifty patients (median age, 74 years; men, n=46, 92%) with echocardiographic evidence of left ventricular hypertrophy (≥12 mm) who underwent endomyocardial biopsy (EMB) and invasive coronary physiological assessments following coronary angiography were enrolled between October 2021 and September 2023 and divided into ATTR-CM (n=30) and non-cardiac amyloidosis (CA) (n=20) groups according to EMB results. All patients with ATTR-CM exhibited positive heart-to-contralateral (H/CL) ratios (&gt;1.5) on technetium 99m pyrophosphate scintigraphy. Fractional flow reserve (FFR), coronary flow reserve (CFR), and index of microcirculatory resistance (IMR) were measured using the PressureWire X guidewire in the left anterior descending artery. Capillary density (/mm2) was determined with EMB tissues by counting the number of CD31 immunopositive luminal structures, whereas the amyloid deposition burden was assessed by measuring the transthyretin immunopositive areas. Circulating cardiac troponin T (hs-cTnT) and brain natriuretic peptide (BNP) were measured.
Results
Compared to the non-CA group, the ATTR-CM group exhibited lower CFR (2.4±0.3 vs. 3.6±0.4, p=0.01), higher IMR (35.4±3.0 vs. 18.7±3.7, p=0.0009), lower capillary density (255.3±24.9 /mm2 vs. 408.6±29.5 /mm2 , p=0.0002), and elevated hs-cTnT levels (0.056±0.006 ng/mL vs. 0.036±0.004 ng/mL, p=0.01), with similar FFR (0.87±0.015 vs. 0.84±0.013, p=0.1) and BNP levels (229.6±38.1 pg/mL vs. 210.2±46.7 pg/mL, p=0.75). In the overall and ATTR-CM groups, capillary density had no significant correlation with IMR (r=0.16, p=0.41 and r=0.04, p=0.84, respectively) and a significant inverse correlation with hs-cTnT (r=-0.47, p=0.001, and r=-0.48, p=0.009, respectively). In the ATTR-CM group, capillary density was not significantly correlated with the H/CL ratio (r=-0.23, p=0.09); nevertheless, transthyretin immunopositive areas were positively correlated with the H/CL ratio (r=0.47, p=0.01).
Conclusion
Capillary rarefaction correlates with elevated hs-cTnT levels but not with elevated IMR, and H/CL ratios, suggesting that CMD is involved at the capillary level in ATTR-CM-related myocardial injury independent of the amyloid deposition burden. -
S Komaki, Y Matsuura, H Tanaka, K Moribayashi, Y Yamamura, K Kurogi, T Ideguchi, N Yamamoto, T Tsuruda, K Kaikita
European Heart Journal 45 ( Supplement_1 ) 2024年10月
記述言語：英語 掲載種別：研究発表ペーパー・要旨（国際会議） 出版者・発行元：Oxford University Press (OUP)
Abstract
Background/Introduction
Patients with acute coronary syndrome (ACS) commonly present with hypertension, diabetes mellitus (DM), and dyslipidaemia as standard modifiable metabolic risk factors. However, little is known about patients with ACS who do not have these risk factors.
Purpose
This study investigated the clinical characteristics and outcomes of patients with ACS without these risk factors who underwent primary percutaneous coronary intervention (PCI).
Methods
This retrospective, single-centre observational study included 1131 consecutive patients with ACS who were admitted to a hospital between January 2013 and May 2021. After excluding patients who did not undergo revascularization or who underwent emergency coronary artery bypass surgery, 947 patients who underwent primary PCI were included in the analysis. Patients were classified into two groups: those with one or more of the following: hypertension, DM, or dyslipidaemia (risk group) and those without any of these factors (non-risk group). Major adverse cardiovascular events (MACE), including all-cause mortality, myocardial infarction (MI), stroke, and heart failure requiring rehospitalisation, were assessed at the 1-year follow-up.
Results
This study classified 78 patients (8.2%) in the non-risk group, who exhibited a significantly lower body mass index (BMI) [23.0 (interquartile range: 21.8–24.7) vs. 23.8 (interquartile range: 21.8–26.2) kg/m2, p = 0.016], compared to the risk group. There were no significant differences in smoking history between the two groups (51.2% vs. 48.9%, p = 0.39). Within 1 year after PCI, MACE occurred in 146 (15.4%) patients (88 [9.2%] with all-cause death, 13 [1.3%] with MI, 23 [2.4%] with stroke, and 27 [2.8%] with heart failure requiring rehospitalisation), with a significantly higher incidence in the non-risk group compared to the risk group (24.4% vs. 14.6%, p = 0.027). Multivariate analysis revealed that both being in the non-risk group and having a low BMI (&lt; 21.5) were independent determinants for the incidence of MACE (hazard ratio [HR]: 1.52; 95% confidence interval [CI]: 1.01–2.29; p = 0.042 and HR: 3.08; 95% CI: 1.30–7.27; p = 0.010, respectively). Kaplan–Meier survival analysis showed a higher MACE rate in the non-risk group than in the risk group (p = 0.009).
Conclusions
Patients with ACS without hypertension, DM, or dyslipidaemia have a poorer prognosis than those with these risk factors, independent of the presence of a lower BMI, and the underlying pathophysiology in this subset of patients needs to be clarified.figure
科研費（文科省・学振・厚労省）獲得実績 【 表示 ／ 非表示 】
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健康寿命延伸を見据えた抗血栓療法のための新規出血リスクスコアの開発
研究課題/領域番号：24K11294 2024年04月 - 2027年03月
独立行政法人日本学術振興会 科学研究費基金 基盤研究(C)
担当区分：研究代表者
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末梢血単球の糖代謝モニタリングを用いた糖尿病性動脈硬化進展予防スキームの構築
研究課題/領域番号：20K17121 2020年04月 - 2023年03月
独立行政法人日本学術振興会 科学研究費補助金 若手研究
担当区分：研究代表者