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キンジヨウ タカヒコ
Kinjiyou Takahiko
金城 貴彦 所属 医学部 医学科（東京女子医科大学病院） 職種 助教 |
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| 論文種別 | 原著 |
| 言語種別 | 英語 |
| 査読の有無 | 査読あり |
| 表題 | Enhanced p122RhoGAP/DLC-1 Expression Can Be a Cause of Coronary Spasm. |
| 掲載誌名 | 正式名：PLoS ONE ISSNコード：1932-6203 |
| 掲載区分 | 国外 |
| 巻・号・頁 | 10(12),pp.e0143884 |
| 著者・共著者 | Kinjo Takahiko,† Tanaka Makoto, Osanai Tomohiro, Shibutani Shuji, Narita Ikuyo, Tanno Tomohiro, Nishizaki Kimitaka, Ichikawa Hiroaki, Kimura Yoshihiro, Ishida Yuji, Yokota Takashi, Shimada Michiko, Homma Yoshimi, Tomita Hirofumi, Okumura Ken* |
| 担当区分 | 筆頭著者 |
| 発行年月 | 2015/12 |
| 概要 | BACKGROUND:We previously showed that phospholipase C (PLC)-δ1 activity was enhanced by 3-fold in patients with coronary spastic angina (CSA). We also reported that p122Rho GTPase-activating protein/deleted in liver cancer-1 (p122RhoGAP/DLC-1) protein, which was discovered as a PLC-δ1 stimulator, was upregulated in CSA patients. We tested the hypothesis that p122RhoGAP/DLC-1 overexpression causes coronary spasm.METHODS AND RESULTS:We generated transgenic (TG) mice with vascular smooth muscle (VSM)-specific overexpression of p122RhoGAP/DLC-1. The gene and protein expressions of p122RhoGAP/DLC-1 were markedly increased in the aorta of homozygous TG mice. Stronger staining with anti-p122RhoGAP/DLC-1 in the coronary artery was found in TG than in WT mice. PLC activities in the plasma membrane fraction and the whole cell were enhanced by 1.43 and 2.38 times, respectively, in cultured aortic vascular smooth muscle cells from homozygous TG compared with those from WT mice. Immediately after ergometrine injection, ST-segment elevation was observed in 1 of 7 WT (14%), 6 of 7 heterozygous TG (84%), and 7 of 7 homozygous TG mice (100%) (p<0.05, WT versus TGs). In the isolated Langendorff hearts, coronary perfusion pressure was increased after ergometrine in TG, but not in WT mice, despite of the similar response to prostaglandin F2α between TG and WT mice (n = 5). Focal narrowing of the coronary artery after ergometrine was documented only in TG mice.CONCLUSIONS:VSM-specific overexpression of p122RhoGAP/DLC-1 enhanced coronary vasomotility after ergometrine injection in mice, which is relevant to human CSA. |
| DOI | 10.1371/journal.pone.0143884 |
| 文献番号 | 26624289 |