The Role of Smooth Muscle Rac1 in Neointimal Formation after Vascular Injury

平滑肌 Rac1 在血管损伤后新内膜形成中的作用

• 批准号: 23790883
• 负责人: LI YUXIN
• 金额: $ 2.75万
• 依托单位: Nihon University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23790883/
• 关键词: 分子血管病態学; 血管障害; 新生内膜; 低分子量Gタンパク質; Rac1; 血管平滑筋細胞

Four weeks after carotid artery ligation, neointimal formation in smRac1+/- mice was substantially reduced compared to control mice. SmRac1+/- SMCs showed decreased chemotaxis, proliferation with decreased phosphorylation of PAK1, ERK, and reduced ROS production compared to that of control SMCs. Furthermore, the expression of cell cycle-associated genes, such as CyclineA, CyclineE, and CDK4 decreased in SMCs from smRac1+/- mice than that in control mice. Moreover, the expression of SM22, a differentiation marker of smooth muscle and highly expressed in differentiated phenotypes of SMCs, was increased in smRac1+/- mice than that in control mice. These results indicate that SMC Rac1 mediates vessel remodeling after intimal injury through inhibition of SMC migration, proliferation and differentiation. Therapeutic modalities, which target Rac1 in SMCs, therefore, may be beneficial in preventing vascular proliferative diseases.

颈动脉连接四周后，与对照小鼠相比，SMRAC1 +/-小鼠的新内膜形成大大降低。与对照SMC相比，SMRAC1 +/- SMC显示趋化性降低，PAK1，ERK磷酸化降低，ROS产生降低。此外，与对照小鼠相比，SMRAC1 +/-小鼠的SMC中与细胞周期相关基因的表达降低了。此外，在SMRAC1 +/-小鼠中，SM22的表达是平滑肌的分化标记和在SMCs的分化表型中高度表达的表达，而不是对照小鼠的表达。这些结果表明，SMC Rac1通过抑制SMC迁移，增殖和分化后介导了内膜损伤后的血管重塑。因此，靶向SMC中Rac1的治疗方法可能有益于预防血管增生性疾病。

项目成果

Effect of pitavastatin on tissue characteristics of atherosclerotic plaque in watanabe heritable hyperlipidemic rabbit: serial observation with IVUS and iMapTM.

匹伐他汀对渡边遗传性高脂血症兔动脉粥样硬化斑块组织特征的影响：IVUS 和 iMapTM 连续观察。

• 发表时间: 2012
• 作者: H. Haruta;T. Hiro;D. Kitano;T. Takayama;Y. Li;A. Hirayama.
• 通讯作者: A. Hirayama.

Plaque-Stabilizing Effect of Atorvastatin Is Stronger for Plaques Evaluated as More Unstable by Angioscopy and Intravenous Ultrasound

• DOI: 10.1253/circj.cj-10-1035
• 发表时间: 2011-06-01
• 期刊: CIRCULATION JOURNAL
• 影响因子: 3.3
• 作者: Hirayama, Atsushi;Saito, Satoshi;Kodama, Kazuhisa
• 通讯作者: Kodama, Kazuhisa

Plaque stabilization by intensive LDL-cholesterol lowering therapy with atorvastatin is delayed in type 2 diabetic patients with coronary artery disease-Serial angioscopic and intravascular ultrasound analysis

患有冠状动脉疾病的 2 型糖尿病患者通过阿托伐他汀强化低密度脂蛋白胆固醇降低治疗实现斑块稳定会延迟 - 系列血管镜和血管内超声分析

• DOI: 10.1016/j.jjcc.2013.01.010
• 发表时间: 2013
• 期刊: J. Cardiol
• 作者: T. Takayama;T. Hiro;Y. Ueda;J. Honye;S. Komatsu;O. Yamaguchi;Y. Li;J. Yajima;K. Takazawa;S. Nanto;S. Saito ;A. Hirayama and K. Kodama
• 通讯作者: A. Hirayama and K. Kodama

Rho Kinase as an Important Mediator of Aortic Stiffness

Rho 激酶作为主动脉僵硬的重要调节因子

• 发表时间: 2011
• 作者: Li Y;et al
• 通讯作者: et al

Rho Kinase as an Important Mediator of Aortic Stiffness.

Rho 激酶是主动脉僵硬的重要调节因子。

• 发表时间: 2011
• 作者: Li Y;Liu PY;Tai HC;Tsai YS;Mitchell GF;Liao JK.
• 通讯作者: Liao JK.