著者

Hiroyuki Ito Tetsuzo Wakatsuki Koji Yamaguchi Daiju Fukuda Yutaka Kawabata Tomomi Matsuura Kenya Kusunose Takayuki Ise Takeshi Tobiume Shusuke Yagi Hirotsugu Yamada Takeshi Soeki Yoshihiro Tsuruo Masataka Sata

出版者

The Japanese Circulation Society

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

pp.CJ-19-0914, (Released:2020-04-10)

参考文献数

37

被引用文献数

1 11

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Background:The coronary adventitia has recently attracted attention as a source of inflammation because it harbors nutrient blood vessels, termed the vasa vasorum (VV). This study assessed the link between local inflammation in adjacent epicardial adipose tissue (EAT) and coronary arterial atherosclerosis in fresh cadavers.Methods and Results:Lesion characteristics in the left anterior descending coronary artery of 10 fresh cadaveric hearts were evaluated using integrated backscatter intravascular ultrasound (IB-IVUS), and the density of the VV and levels of inflammatory molecules from the adjacent EAT were measured for each of the assessed lesions. The lesions were divided into lipid-rich, lipid-moderate, and lipid-poor groups according to percentage lipid volume assessed by IB-IVUS. Higher expression of inflammatory molecules (i.e., vascular endothelial growth factor A [VEGFA] andVEGFB) was observed in adjacent EAT of lipid-rich (n=11) than in lipid-poor (n=11) lesions (7.99±3.37 vs. 0.45±0.85 arbitrary units [AU], respectively, forVEGFA; 0.27±0.15 vs. 0.11±0.07 AU, respectively, forVEGFB; P<0.05). The density of adventitial VV was greater in lipid-rich than lipid-poor lesions (1.50±0.58% vs. 0.88±0.23%; P<0.05).Conclusions:Lipid-rich coronary plaques are associated with adventitial VV and local inflammation in adjacent EAT in fresh cadavers. This study suggests that local inflammation of EAT is associated with coronary plaque progression via the VV.

著者

Hiroya Hayashi Yasuhiro Izumiya Toshifumi Ishida Yuichiro Arima Ou Hayashi Minoru Yoshiyama Kenichi Tsujita Daiju Fukuda

出版者

The Japanese Circulation Society

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

pp.CJ-23-0353, (Released:2023-11-25)

参考文献数

43

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Background: Resistance exercise is beneficial in patients with lower extremity arterial disease. Muscle-derived exosomes contain many types of signaling molecules, including microRNAs (miRNAs). Here, we tested the hypothesis that exosomal miRNAs secreted by growing muscles promote an angiogenic response in endothelial cells (ECs).Methods and Results: Skeletal muscle-specific conditional Akt1 transgenic (Akt1-TG) mice, in which skeletal muscle growth can be induced were used as a model of resistance training. Remarkable skeletal muscle growth was observed in mice 2 weeks after gene activation. The protein amount in exosomes secreted by growing muscles did not differ between Akt1-TG and control mice. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway frequency analysis of 4,665 target genes, identified using an miRNA array miRNAs, revealed a significant increase in Akt and its downstream signaling pathway genes. Among the upregulated miRNAs, miR1, miR133, and miR206 were significantly upregulated in the serum of Akt1-TG mice. miR206 was also increased in insulin-like growth factor (IGF)-1-stimulated hypertrophied myotubes. Exogenous supplementation of exosomal miR206 to human umbilical vein ECs promoted angiogenesis, as assessed using the spheroid assay, and increased the expression of angiogenesis-related transcripts.Conclusions: Exosomal miR206 is upregulated in the blood of Akt1-TG mice and in IGF-stimulated cultured myotubes. Exogenous supplementation of miR206 promoted an angiogenic response in ECs. Our data suggest that miR206 secreted from growing muscles acts on ECs and promotes angiogenesis.

著者

Kenya Kusunose Yuta Torii Hirotsugu Yamada Susumu Nishio Yukina Hirata Yoshihito Saijo Takayuki Ise Koji Yamaguchi Daiju Fukuda Shusuke Yagi Takeshi Soeki Tetsuzo Wakatsuki Masataka Sata

出版者

The Japanese Circulation Society

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

pp.CJ-19-0663, (Released:2019-10-12)

参考文献数

27

被引用文献数

6

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Background:Whether preoperative echocardiography improves postoperative outcomes is not well established, so we examined the value of echocardiographic assessment on the onset of postoperative heart failure (HF), and determining which patients benefitted most from undergoing echocardiography prior to major elective non-cardiac surgery.Methods and Results:We identified all patients aged 50 years and older who had major elective non-cardiac surgery, and excluded patients with previously identified severe cardiovascular disease. The primary endpoint was the onset of HF during hospitalization. A total of 806 patients were included in the analysis. During hospitalization, 49 patients (6%) reached the primary endpoint. Within the matched cohort, preoperative echocardiography was associated with a statistically significant decrease in postoperative HF (hazard ratio: 0.46, P=0.01). In subgroup analyses, age, sex, body surface area, hypertension, diabetes mellitus, prior HF, surgical type, chronic kidney disease, pulmonary disease, and malignancy influenced the association of echocardiography with postoperative HF.Conclusions:The use of echocardiography in elderly patients with certain risk factors was associated with improved postoperative outcomes. The basis for this finding remains to be determined; particularly whether echocardiography is simply a marker of a population with better outcomes or whether it leads to better management that improves outcomes.

著者

Arief Rahadian Daiju Fukuda Hotimah Masdan Salim Shusuke Yagi Kenya Kusunose Hirotsugu Yamada Takeshi Soeki Masataka Sata

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

vol.27, no.11, pp.1141-1151, 2020-11-01 (Released:2020-11-01)

参考文献数

43

被引用文献数

22 44

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Aim: Recent studies have demonstrated that selective sodium–glucose cotransporter 2 inhibitors (SGLT2is) reduce cardiovascular events, although their mechanism remains obscure. We examined the effect of canagliflozin, an SGLT2i, on atherogenesis and investigated its underlying mechanism. Method: Canagliflozin (30 mg/kg/day) was administered by gavage to streptozotocin-induced diabetic apolipoprotein E-deficient (ApoE-/-) mice. Sudan IV staining was performed at the aortic arch. Immunostaining, quantitative RT-PCR, and vascular reactivity assay were performed using the aorta. In vitro experiments using human umbilical vein endothelial cells (HUVECs) were also performed. Result: Canagliflozin decreased blood glucose (P<0.001) and total cholesterol (P<0.05) levels. Sudan IV staining showed that 12-week canagliflozin treatment decreased atherosclerotic lesions (P<0.05). Further, 8-week canagliflozin treatment ameliorated endothelial dysfunction, as determined by acetylcholine-induced vasodilation (P<0.05), and significantly reduced the expressions of inflammatory molecules such as ICAM-1 and VCAM-1 in the aorta at the RNA and protein levels. Canagliflozin also reduced the expressions of NADPH oxidase subunits such as NOX2 and p22phox in the aorta and reduced urinary excretion of 8-OHdG, suggesting a reduction in oxidative stress. Methylglyoxal, a precursor of advanced glycation end products, increased the expressions of ICAM-1 and p22phox in HUVECs (P<0.05, both). Methylglyoxal also decreased the phosphorylation of eNOSSer1177 and Akt but increased the phosphorylation of eNOSThr495 and p38 MAPK in HUVECs. Conclusion: Canagliflozin prevents endothelial dysfunction and atherogenesis in diabetic ApoE-/- mice. Anti-inflammatory and antioxidative potential due to reduced glucose toxicity to endothelial cells might be its underlying mechanisms.

著者

Daiju Fukuda Phuong Tran Pham Masataka Sata

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.RV17059, (Released:2021-07-12)

参考文献数

82

被引用文献数

4

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Sterile chronic inflammation causes cardiometabolic disorders; however, the mechanisms are not fully understood. Previous studies have demonstrated the degradation of cells/tissues in the vasculature and metabolic organs in lifestyle-associated diseases, such as diabetes and hyperlipidemia, suggesting the release and/or accumulation of nucleic acids from damaged cells. DNA is indispensable for life; however, DNA fragments, especially those from pathogens, strongly induce inflammation by the activation of DNA sensors. Growing evidence suggests that DNA-sensing mechanisms, which are normally involved in self-defense against pathogens as the innate immune system, are associated with the progression of inflammatory diseases in response to endogenous DNA fragments. There are several types of DNA sensors in our bodies. Toll-like receptor 9 (TLR9)—one of the most studied DNA sensors—recognizes DNA fragments in endosome. In addition, stimulator of interferon genes (STING), which has recently been extensively investigated, recognizes cyclic GMP-AMP (cGAMP) generated from DNA fragments in the cytosol. Both TLR9 and STING are known to play pivotal roles in host defense as the innate immune system. However, recent studies have indicated that the activation of these DNA sensors in immune cells, such as macrophages, promotes inflammation leading to the development of vascular and metabolic diseases associated with lifestyle. In this review, we discuss recent advances in determining the roles of DNA sensors in these disease contexts. Revealing a novel mechanism of sterile chronic inflammation regulated by DNA sensors might facilitate clinical interventions for these health conditions.

著者

Shusuke Yagi Ken-ichi Aihara Daiju Fukuda Akira Takashima Tomoya Hara Junko Hotchi Takayuki Ise Koji Yamaguchi Takeshi Tobiume Takashi Iwase Hirotsugu Yamada Takeshi Soeki Tetsuzo Wakatsuki Michio Shimabukuro Masashi Akaike Masataka Sata

出版者

一般社団法人 日本動脈硬化学会

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.26914, (Released:2014-10-24)

参考文献数

29

被引用文献数

8 29

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Aim: The consumption of n-3 polyunsaturated fatty acids (PUFA), including docosahexaenoic acid DHA), reduces the incidence of cardiovascular events, and reduced serum levels of n-3 PUFA may be associated with an increased risk of cardiovascular events. However, controversy remains regarding which components of PUFA are associated with the endothelial function in patients with coronary artery disease (CAD). We therefore examined the associations between the n-3 and n-6 PUFA levels and CAD.Methods: We retrospectively reviewed 160 consecutive Japanese patients with CAD whose endothelial function was measured according to the percent change in flow-mediated dilation (FMD) and the serum levels of n-3 PUFA, including eicosapentaenoic acid (EPA) and DHA, and n-6 PUFA, including arachidonic acid (AA) and dihomo-gamma-linolenic acid (DHLA).Results: A single regression analysis showed no relationships between the FMD and the serum levels of PUFA, including EPA, DHA, AA and DHLA. In contrast, a multiple regression analysis showed that the DHA level was a positive (P<0.01) and age was a negative (P<0.001) contributor to an increased FMD; however, sex, body mass index, systolic and diastolic blood pressure, current/past smoking and the levels of HbA1c, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, EPA, AA and DHLA did not significantly affect the outcome.Conclusions: The serum level of DHA is associated with the endothelial function evaluated according to the FMD in patients with CAD, thus suggesting that a low serum level of DHA may be a predictive biomarker for endothelial dysfunction.