- 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
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
- Shinobu Sugihara Ichiro Hisatome Masanari Kuwabara Koichiro Niwa Nani Maharani Masahiko Kato Kazuhide Ogino Toshihiro Hamada Haruaki Ninomiya Yukihito Higashi Kimiyoshi Ichida Kazuhiro Yamamoto
- 出版者
- The Japanese Circulation Society
- 雑誌
- Circulation Journal (ISSN:13469843)
- 巻号頁・発行日
- vol.79, no.5, pp.1125-1132, 2015-04-24 (Released:2015-04-24)
- 参考文献数
- 41
- 被引用文献数
- 24 82
Background:Uric acid (UA) serves as an antioxidant in vascular endothelial cells. UA transporter 1 (URAT1) encoded by SLC22A12 is expressed in the kidney and vessels and its loss of function causes hypouricemia. The purpose of this study was to examine whether there is any endothelial dysfunction in patients with hypouricemia.Methods and Results:Twenty-six patients with hypouricemia (<2.5 mg/dl) and 13 healthy control subjects were enrolled. Endothelial function was evaluated using flow-mediated dilation (FMD). mRNA of UA transporters expressed in cultured human umbilical endothelial cells (HUVEC) was detected on RT-PCR. There was a positive correlation between FMD and serum UA in the hypouricemia group. URAT1 loss-of-function mutations were found in the genome of 21 of 26 patients with hypouricemia, and not in the other 5. In the hypouricemia groups, serum UA in homozygous and compound heterozygous patients was significantly lower than in other groups, suggesting that severity of URAT1 dysfunction may influence the severity of hypouricemia. Thirteen of 16 hypouricemia subjects with homozygous and compound heterozygote mutations had SUA <0.8 mg/dl and their FMD was lower than in other groups. HUVEC do not express mRNA of URAT1, suggesting the null role of URAT1 in endothelial function.Conclusions:Depletion of UA due to SLC22A12/URAT1 loss-of-function mutations causes endothelial dysfunction in hypouricemia patients. (Circ J 2015; 79: 1125–1132)
- 著者
- Shinobu Sugihara Ichiro Hisatome Masanari Kuwabara Koichiro Niwa Nani Maharani Masahiko Kato Kazuhide Ogino Toshihiro Hamada Haruaki Ninomiya Yukihito Higashi Kimiyoshi Ichida Kazuhiro Yamamoto
- 出版者
- 日本循環器学会
- 雑誌
- Circulation Journal (ISSN:13469843)
- 巻号頁・発行日
- pp.CJ-14-1267, (Released:2015-02-23)
- 参考文献数
- 41
- 被引用文献数
- 10 82
Background:Uric acid (UA) serves as an antioxidant in vascular endothelial cells. UA transporter 1 (URAT1) encoded by SLC22A12 is expressed in the kidney and vessels and its loss of function causes hypouricemia. The purpose of this study was to examine whether there is any endothelial dysfunction in patients with hypouricemia.Methods and Results:Twenty-six patients with hypouricemia (<2.5 mg/dl) and 13 healthy control subjects were enrolled. Endothelial function was evaluated using flow-mediated dilation (FMD). mRNA of UA transporters expressed in cultured human umbilical endothelial cells (HUVEC) was detected on RT-PCR. There was a positive correlation between FMD and serum UA in the hypouricemia group. URAT1 loss-of-function mutations were found in the genome of 21 of 26 patients with hypouricemia, and not in the other 5. In the hypouricemia groups, serum UA in homozygous and compound heterozygous patients was significantly lower than in other groups, suggesting that severity of URAT1 dysfunction may influence the severity of hypouricemia. Thirteen of 16 hypouricemia subjects with homozygous and compound heterozygote mutations had SUA <0.8 mg/dl and their FMD was lower than in other groups. HUVEC do not express mRNA of URAT1, suggesting the null role of URAT1 in endothelial function.Conclusions:Depletion of UA due to SLC22A12/URAT1 loss-of-function mutations causes endothelial dysfunction in hypouricemia patients.