Pathogenesis and molecular mechanisms of arteral restenosis

动脉再狭窄的发病机制和分子机制

• 批准号: 06454287
• 负责人: NAGAI Ryozo
• 金额: $ 4.99万
• 依托单位: Gunma University School of Medicine (1995)The University of Tokyo (1994)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06454287/
• 关键词: RESTENOSIS,; SMOOTH MUSCLE,; MYOSIN,; SM1; 2 GENE,; SMemb GENE,; TRANSCRIPTION FACTOR,; PTCA; 転写因子; ミオシン重鎖; 遺伝子転写; 形質変換

We previously demonstrated that rabbit and rat smooth muscles contain at least three types of MHCs ; SM1(204kDa), SM2(200kDa)and SMemb(200kDa). SM1 and SM2 are two smooth muscle specific MHC isoforms arising from a singlegene, and SMemb is a third type of MHC isoform abundantly expressed in embryonic aortas. The expression of three MHC isoforms is developmentallyregulated.The presence of developmentallyregulated MHC isoforms in vascular smooth muscles provides importantmoleculartools to investigate the molecularmechanism underlying vascular diseases. We first demonstrated that the developmentalregulation of myosin heavy chain expression occurs in proliferating smooth muscle cells after percutaneous angioplasty(PTCA) ; SMemb was reexpressed and SM2 was downregulated. We therefore characterized the promoter region of the SM1/2 and SMemb genes. In this study, we identified an important cis element for the SMemb gene and a transcription factor, BTEB-2, which coordinately regulate the SMemb gene.We furthermore characterized SM1/2 gene which is most specifically expressed in smooth muscles. SM1/2 gene harbors two CCTCCC elements-80 bp upstream of the transcription initiation site. These elements play a basic role for SM1/2 gene transcription but does not necessarily regulate smooth muscle-specific expression.

我们之前证明兔子和大鼠的平滑肌至少含有三种类型的 MHC； SM1(204kDa)、SM2(200kDa)和SMemb(200kDa)。 SM1 和 SM2 是由单个基因产生的两种平滑肌特异性 MHC 同工型，SMemb 是在胚胎主动脉中大量表达的第三种类型的 MHC 同工型。三种 MHC 同工型的表达受到发育调节。血管平滑肌中发育调节的 MHC 同工型的存在为研究血管疾病的分子机制提供了重要的分子工具。我们首先证明了肌球蛋白重链表达的发育调节发生在经皮血管成形术（PTCA）后增殖的平滑肌细胞中； SMemb 重新表达，SM2 下调。因此，我们对 SM1/2 和 SMemb 基因的启动子区域进行了表征。在本研究中，我们鉴定了 SMemb 基因的一个重要顺式元件和协调调节 SMemb 基因的转录因子 BTEB-2。我们进一步表征了在平滑肌中最特异表达的 SM1/2 基因。 SM1/2 基因在转录起始位点上游 80 bp 处包含两个 CCTCCC 元件。这些元件对 SM1/2 基因转录发挥基本作用，但不一定调节平滑肌特异性表达。

项目成果

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Suzuki T,Katoh H,Suzuki S,Ohtaki E,Watanabe M,Yazaki Y,Nagai R.: "A novel biochemical diagnostic method for aortic dissection-the results of a prospective study using an immunoassay of smooth muscle myosin heavy chain." Circulation. (in press.).

Suzuki T，Katoh H，Suzuki S，Ohtaki E，Watanabe M，Yazaki Y，Nagai R.：“主动脉夹层的新型生化诊断方法 - 使用平滑肌肌球蛋白重链免疫测定的前瞻性研究结果。”

Okamoto E. et: "Diversity of the synthetic-state smooth muscle cells proliferating in mechanically and hemodynamically injured arteries" Lab. Invest. 74. 120-128 (1996)

Okamoto E. 等人：“在机械和血流动力学损伤的动脉中增殖的合成状态平滑肌细胞的多样性”实验室。

Kurihara Y,Kurihara H,Oda H,Maemura K,Nagai R,Ishikawa T,Yazaki Y.: "Aortic arch malformations and ventricular septal defect in mice deficient in endothelin-1." J Clin Invest. 96. 293-300 (1995)

Kurihara Y、Kurihara H、Oda H、Maemura K、Nagai R、Ishikawa T、Yazaki Y.：“内皮素-1 缺陷小鼠的主动脉弓畸形和室间隔缺损。”

Kojima M.,et al: "Angiotensin II receptor antagonist TCV 116 regresses hypertensive left ventricular hypertrophy in vivo and inhibits intracellular signaling pathway of stretch-medioted cardiomyocyte hypertrophy in vitro" Circulation. 89. 2204-2211 (1994)

Kojima M.等人：“血管紧张素 II 受体拮抗剂 TCV 116 可在体内消退高血压左心室肥大，并在体外抑制拉伸介导的心肌细胞肥大的细胞内信号传导途径”循环。