- 著者
- Takuo Emoto Naoto Sasaki Tomoya Yamashita Kazuyuki Kasahara Keiko Yodoi Yoshihiro Sasaki Takuya Matsumoto Taiji Mizoguchi Ken-ichi Hirata
- 出版者
- 日本循環器学会
- 雑誌
- Circulation Journal (ISSN:13469843)
- 巻号頁・発行日
- vol.78, no.12, pp.2935-2941, 2014-11-25 (Released:2014-11-25)
- 参考文献数
- 22
- 被引用文献数
- 9 40
Background:The protective function of regulatory T cells (Treg) has been identified in experimental atherosclerosis, but the contribution of Tregto the pathogenesis of human coronary artery disease (CAD) remains poorly understood. We investigated Tregand regulatory T-cell/effector T-cell (Treg/Teff) ratio in peripheral blood samples from CAD patients using a new strategy for precise identification of Treg.Methods and Results:Peripheral blood samples were collected from 73 stable CAD patients (55 middle-aged CAD patients and 18 old CAD patients) and 64 controls (47 middle-aged controls and 17 young controls). CD3+CD4+FoxP3+T cells were divided into 3 fractions: CD45RA+FoxP3lowresting Treg(Fr1), CD45RA–FoxP3highactivated Treg(Fr2), and CD45RA–FoxP3lownon-Treg(Fr3). CAD patients had lower percentages of Fr1 and Fr2 and higher percentages of Fr3 and CD45RA–Foxp3–Teff(Fr4+5) within the CD3+CD4+T-cell population compared to age-matched controls. Treg/Teffratio (Fr1+2/Fr3+4+5) in CAD patients was also markedly lower than in controls (middle-aged control, 0.17±0.09 vs. middle-aged CAD, 0.10±0.05; P<0.001). The percentage of CD4+CD28nullT cells within the CD4+T-cell population was negatively correlated with Treg/Teffratio, excluding CD4+CD28nullT cells <0.3% (r=–0.27, P<0.05). High-sensitivity C-reactive protein was also negatively correlated with Treg/Teffratio (r=–0.22, P<0.05).Conclusions:CAD patients had reduced Tregand Treg/Teffratio compared to healthy controls. The present findings may be helpful when developing immunotherapy for the prevention of CAD. (Circ J 2014; 78: 2935–2941)
- 著者
- Tomohiro Hayashi Tomoya Yamashita Hikaru Watanabe Kenjiro Kami Naofumi Yoshida Tokiko Tabata Takuo Emoto Naoto Sasaki Taiji Mizoguchi Yasuhiro Irino Ryuji Toh Masakazu Shinohara Yuko Okada Wataru Ogawa Takuji Yamada Ken-ichi Hirata
- 出版者
- The Japanese Circulation Society
- 雑誌
- Circulation Journal (ISSN:13469843)
- 巻号頁・発行日
- vol.83, no.1, pp.182-192, 2018-12-25 (Released:2018-12-25)
- 参考文献数
- 44
- 被引用文献数
- 79
Background: Gut microbiome composition or circulating microbiome-related metabolites in patients with heart failure (HF) have not been investigated at different time points (i.e., in the decompensated (Decomp) and compensated (Comp) phases). Methods and Results: We prospectively enrolled 22 patients admitted for HF and 11 age-, sex-, and comorbidity-matched hospitalized control subjects without a history of HF. Gut flora and plasma microbiome-related metabolites were evaluated by amplicon sequencing of the bacterial 16S ribosomal RNA gene and capillary electrophoresis time-of-flight mass spectrometry, respectively. HF patients were evaluated in both the Decomp and Comp phases during hospitalization. The phylum Actinobacteria was enriched in HF patients compared with control subjects. At the genus level, Bifiodobacterium was abundant while Megamonas was depleted in HF patients. Meanwhile, plasma concentration of trimethylamine N-oxide (TMAO), a gut microbiome-derived metabolite, was increased in HF patients (Decomp HF vs. control, P=0.003; Comp HF vs. control, P=0.004). A correlation analysis revealed positive correlations between the abundance of the genus Escherichia/Shigella and levels of TMAO and indoxyl sulfate (IS, a microbe-dependent uremic toxin) in Comp HF (TMAO: r=0.62, P=0.002; IS: r=0.63, P=0.002). Escherichia/Shigella was more abundant in Decomp than in Comp HF (P=0.030). Conclusions: Our results suggest that gut microbiome composition and microbiome-related metabolites are altered in HF patients.
- 著者
- Tomoya Yamashita Kazuyuki Kasahara Takuo Emoto Takuya Matsumoto Taiji Mizoguchi Naoki Kitano Naoto Sasaki Ken-ichi Hirata
- 出版者
- 日本循環器学会
- 雑誌
- Circulation Journal (ISSN:13469843)
- 巻号頁・発行日
- vol.79, no.9, pp.1882-1890, 2015-08-25 (Released:2015-08-25)
- 参考文献数
- 48
- 被引用文献数
- 4 49
Atherosclerosis is considered a chronic inflammatory disease and an intervention targeting the inflammatory process could be a new therapeutic strategy for preventing atherosclerotic cardiovascular diseases (CVD). We hypothesized that the intestine, which is considered the biggest immune organ in the human body, could be a therapeutic target for preventing CVD. We demonstrated that oral administration of anti-CD3 antibody or an active form of vitamin D3reduced atherosclerosis in mice via induction of regulatory T cells and tolerogenic dendritic cells in the gut-associated lymphoid tissues. Similar to regulatory immune responses achieved by oral tolerance, our method had systemic effects that ultimately contributed towards atherosclerosis reduction. Recently, we have been interested in the gut microbiota, which have been reported as highly associated with intestinal immunity and systemic metabolic disorders, including obesity and diabetes. Notably, the guts of obese individuals are predominantly colonized byFirmicutesoverBacteroidetes. The association between atherosclerosis and microbiota has been attracting increased attention, and gut microbiota have been shown to participate in the metabolism of a proatherogenic compound called trimethylamine-N-oxide (TMAO) and aggravate CVD. Our investigation of the relationship between susceptibility to CVD and the gut microbiota revealed a characteristic flora type. Here, we discuss the evidence for the relationship between the gut microbiota and cardiometabolic diseases, and consider the gut microbiota as new potential therapeutic targets for treating CVD. (Circ J 2015; 79: 1882–1890)
- 著者
- Takuo Emoto Naoto Sasaki Tomoya Yamashita Kazuyuki Kasahara Keiko Yodoi Yoshihiro Sasaki Takuya Matsumoto Taiji Mizoguchi Ken-ichi Hirata
- 出版者
- 日本循環器学会
- 雑誌
- Circulation Journal (ISSN:13469843)
- 巻号頁・発行日
- pp.CJ-14-0644, (Released:2014-10-18)
- 参考文献数
- 22
- 被引用文献数
- 9 40
Background:The protective function of regulatory T cells (Treg) has been identified in experimental atherosclerosis, but the contribution of Tregto the pathogenesis of human coronary artery disease (CAD) remains poorly understood. We investigated Tregand regulatory T-cell/effector T-cell (Treg/Teff) ratio in peripheral blood samples from CAD patients using a new strategy for precise identification of Treg.Methods and Results:Peripheral blood samples were collected from 73 stable CAD patients (55 middle-aged CAD patients and 18 old CAD patients) and 64 controls (47 middle-aged controls and 17 young controls). CD3+CD4+FoxP3+T cells were divided into 3 fractions: CD45RA+FoxP3lowresting Treg(Fr1), CD45RA–FoxP3highactivated Treg(Fr2), and CD45RA–FoxP3lownon-Treg(Fr3). CAD patients had lower percentages of Fr1 and Fr2 and higher percentages of Fr3 and CD45RA–Foxp3–Teff(Fr4+5) within the CD3+CD4+T-cell population compared to age-matched controls. Treg/Teffratio (Fr1+2/Fr3+4+5) in CAD patients was also markedly lower than in controls (middle-aged control, 0.17±0.09 vs. middle-aged CAD, 0.10±0.05; P<0.001). The percentage of CD4+CD28nullT cells within the CD4+T-cell population was negatively correlated with Treg/Teffratio, excluding CD4+CD28nullT cells <0.3% (r=–0.27, P<0.05). High-sensitivity C-reactive protein was also negatively correlated with Treg/Teffratio (r=–0.22, P<0.05).Conclusions:CAD patients had reduced Tregand Treg/Teffratio compared to healthy controls. The present findings may be helpful when developing immunotherapy for the prevention of CAD.