著者

Katsushige Ono Yu-ki Iwasaki Masaharu Akao Takanori Ikeda Kuniaki Ishii Yasuya Inden Kengo Kusano Yoshinori Kobayashi Yukihiro Koretsune Tetsuo Sasano Naokata Sumitomo Naohiko Takahashi Shinichi Niwano Nobuhisa Hagiwara Ichiro Hisatome Tetsushi Furukawa Haruo Honjo Toru Maruyama Yuji Murakawa Masahiro Yasaka Eiichi Watanabe Takeshi Aiba Mari Amino Hideki Itoh Hisashi Ogawa Yasuo Okumura Chizuko Aoki-Kamiya Jun Kishihara Eitaro Kodani Takashi Komatsu Yusuke Sakamoto Kazuhiro Satomi Tsuyoshi Shiga Tetsuji Shinohara Atsushi Suzuki Shinya Suzuki Yukio Sekiguchi Satoshi Nagase Noriyuki Hayami Masahide Harada Tadashi Fujino Takeru Makiyama Mitsunori Maruyama Junichiro Miake Shota Muraji Hiroshige Murata Norishige Morita Hisashi Yokoshiki Koichiro Yoshioka Kenji Yodogawa Hiroshi Inoue Ken Okumura Takeshi Kimura Hiroyuki Tsutsui Wataru Shimizu on behalf of the Japanese Circulation Society and Japanese Heart Rhythm Society Joint Working Group

出版者

The Japanese Circulation Society

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

pp.CJ-20-1212, (Released:2022-03-11)

参考文献数

998

被引用文献数

44

著者

Maya Adachi Mai Watanabe Yasutaka Kurata Yumiko Inoue Tomomi Notsu Kenshiro Yamamoto Hiromu Horie Shogo Tanno Maki Morita Junichiro Miake Toshihiro Hamada Masanari Kuwabara Naoe Nakasone Haruaki Ninomiya Motokazu Tsuneto Yasuaki Shirayoshi Akio Yoshida Motonobu Nishimura Kazuhiro Yamamoto Ichiro Hisatome

出版者

The Japanese Circulation Society

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

pp.CJ-19-0261, (Released:2019-09-13)

参考文献数

39

被引用文献数

5

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Background:Treatment of myocardial infarction (MI) includes inhibition of the sympathetic nervous system (SNS). Cell-based therapy using adipose-derived stem cells (ASCs) has emerged as a novel therapeutic approach to treat heart failure in MI. The purpose of this study was to determine whether a combination of ASC transplantation and SNS inhibition synergistically improves cardiac functions after MI.Methods and Results:ASCs were isolated from fat tissues of Lewis rats. In in vitro studies using cultured ASC cells, mRNA levels of angiogenic factors under normoxia or hypoxia, and the effects of norepinephrine and a β-blocker, carvedilol, on the mRNA levels were determined. Hypoxia increased vascular endothelial growth factor (VEGF) mRNA in ASCs. Norepinephrine further increased VEGF mRNA; this effect was unaffected by carvedilol. VEGF promoted VEGF receptor phosphorylation and tube formation of human umbilical vein endothelial cells, which were inhibited by carvedilol. In in vivo studies using a rat MI model, transplanted ASC sheets improved contractile functions of MI hearts; they also facilitated neovascularization and suppressed fibrosis after MI. These beneficial effects of ASC sheets were abolished by carvedilol. The effects of ASC sheets and carvedilol on MI heart functions were confirmed by Langendorff perfusion experiments using isolated hearts.Conclusions:ASC sheets prevented cardiac dysfunctions and remodeling after MI in a rat model via VEGF secretion. Inhibition of VEGF effects by carvedilol abolished their beneficial effects.

著者

Keiko Nagata Kazuhiko Hayashi Keisuke Kumata Yukio Satoh Mitsuhiko Osaki Yuji Nakayama Satoshi Kuwamoto Yoshinori Ichihara Tsuyoshi Okura Kazuhiko Matsuzawa Junichiro Miake Shuji Fukata Takeshi Imamura

出版者

The Japan Endocrine Society

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

pp.EJ22-0609, (Released:2023-03-10)

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Epstein-Barr virus (EBV) is a human herpes virus that latently infects B lymphocytes. When EBV is reactivated, host B cells differentiate into plasma cells and produce IgM-dominant antibodies as well as many progeny virions. The aims of the present study were to confirm the IgM dominance of thyrotropin-receptor antibodies (TRAbs) produced by EBV reactivation and investigate the roles of TRAb-IgM in Graves’ disease. Peripheral blood mononuclear cells (PBMCs) containing TRAb-producing cells were stimulated for EBV reactivation, and TRAb-IgM and TRAb-IgG were measured by ELISA. TRAb-IgM were purified and TSH-binding inhibitory activities were assessed using a radio-receptor assay. Porcine thyroid follicular epithelial cells were cultured with TRAb-IgM and/or complements to measure the intracellular levels of cAMP and the amount of LDH released. TRAb-IgM/TRAb-IgG (the MG ratio) was examined in sequential serum samples of Graves’ disease and compared among groups of thyroid function. The results obtained showed that IgM-dominant TRAb production was induced by EBV reactivation. TRAb-IgM did not inhibit TSH binding to TSH receptors and did not transduce hormone-producing signals. However, it destroyed thyroid follicular epithelial cells with complements. The MG ratio was significantly higher in samples of hyperthyroidism or hypothyroidism than in those with normal function or in healthy controls. A close relationship was observed between TRAb-IgM produced by EBV reactivation and the development and exacerbation of Graves’ disease. The present results provide novel insights for the development of prophylaxis and therapeutics for Graves’ disease.

著者

Fikri Taufiq Peili Li Junichiro Miake Ichiro Hisatome

出版者

The Japanese Circulation Society

雑誌

Circulation Reports (ISSN:24340790)

巻号頁・発行日

vol.1, no.11, pp.469-473, 2019-11-08 (Released:2019-11-08)

参考文献数

54

被引用文献数

8

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Among the several independent risk factors for atrial fibrillation (AF), hyperuricemia has been widely accepted as associated with the incidence of paroxysmal or persistent AF, as well as with the risk of AF in patients undergoing cardiovascular surgery. The electrophysiological mechanism of AF involves electrical remodeling of the arrhythmogenic substrate and abnormal automaticity as trigger. Both electrical and structural remodeling mediated by oxidative stress derived from either xanthine oxidoreductase (XOR), soluble uric acid (UA) or monosodium urate (MSU) crystals might be plausible explanations for the association of AF with hyperuricemia. XOR generates reactive oxygen species (ROS) that lead to atrial structural remodeling via inflammation. Soluble UA accumulates intracellularly through UA transporters (UAT), shortening the atrial action potential via enhanced expression and activity of Kv1.5 channel proteins. Intracellular accumulation of soluble UA generates ROS in atrial myocytes via nicotinamide adenine dinucleotide phosphate oxidase, which phosphorylates ERK/Akt and heat shock factor 1 (HSF1), thereby increasing transcription and translation of Hsp70, which stabilizes Kv1.5. In macrophages, MSU activates the NLRP3 inflammasome and proteolytic processing mediated by caspase-1 with enhanced interleukin (IL)-1β and IL-18 secretion. Use of an XOR inhibitor, antioxidants, a UAT inhibitor such as a uricosuric agent, and an NLRP3 inflammasome inhibitor, might become a potential strategy to reduce the risk of hyperuricemia-induced AF, and control serum UA level.

著者

Hiroshi Fujii Yu Ikeuchi Yasutaka Kurata Nobuhito Ikeda Udin Bahrudin Peili Li Yuji Nakayama Ryo Endo Akira Hasegawa Kumi Morikawa Junichiro Miake Akio Yoshida Kyoko Hidaka Takayuki Morisaki Haruaki Ninomiya Yasuaki Shirayoshi Kazuhiro Yamamoto Ichiro Hisatome

出版者

日本循環器学会

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

pp.CJ-12-0126, (Released:2012-09-04)

参考文献数

27

被引用文献数

3 2

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Background: The prion protein (PrP) has been reported to serve as a surface maker for isolation of cardiomyogenic progenitors from murine embryonic stem (ES) cells. Although PrP-positive cells exhibited automaticity, their electrophysiological characteristics remain unresolved. The aim of the present study was therefore to investigate the electrophysiological properties of PrP-positive cells in comparison with those of HCN4p-or Nkx2.5-positive cells. Methods and Results: Differentiation of AB1, HCN5p-EGFP and hcgp7 ES cells into cardiac progenitors was induced by embryoid body (EB) formation. EBs were dissociated and cells expressing PrP, HCN4-EGFP and/or Nkx2.5-GFP were collected via flow cytometry. Sorted cells were subjected to reverse transcriptase-polymerase chain reaction, immunostaining and patch-clamp experiments. PrP-positive cells expressed mRNA of undifferentiation markers, first and second heart field markers, and cardiac-specific genes and ion channels, indicating their commitment to cardiomyogenic progenitors. PrP-positive cells with automaticity showed positive and negative chronotropic responses to isoproterenol and carbamylcholine, respectively. Hyperpolarization-activated cation current (If) was barely detectable, whereas Na+ and L-type Ca2+ channel currents were frequently observed. Their spontaneous activity was slowed by inhibition of sarcoplasmic reticulum Ca2+ uptake and release but not by blocking If. The maximum diastolic potential of their spontaneous firings was more depolarized than that of Nkx2.5-GFP-positive cells. Conclusions: PrP-positive cells contained cardiac progenitors that separated from the lineage of sinoatrial node cells. PrP can be used as a marker to enrich nascent cardiac progenitors.