Reduction of intimal hyperplasia: G Beta gama inhibitor

减少内膜增生：G Beta gama 抑制剂

• 批准号: 6668138
• 负责人: JASON A PETROFSKI
• 金额: $ 4.62万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6668138
• 关键词: Adenoviridae; G protein; G protein coupled receptor kinase; artery stenosis; beta adrenergic receptor kinase; biological signal transduction; blood vessel transplantation; cell migration; cell proliferation; coronary artery; coronary bypass; coronary disorder; coronary vessels; disease /disorder model; enzyme activity; enzyme inhibitors; gene expression; hyperplasia; mitogen activated protein kinase; model design /development; muscle cells; protein structure function; swine; tissue /cell culture; transfection /expression vector; vascular smooth muscle

Vein graft intimal hyperplasia involves an abnormal migration and proliferation of vascular smooth muscle (VSM) cells. The end result is a thickening of the intima, reduced luminal area and potential for thrombotic occlusion. This process limits the effectiveness of reversed saphenous vein graft bypass as a treatment of coronary artery stenosis. VSM proliferation may be dependent on signal transduction, which involves Gbeta gamma subunits. The beta-adrenergic receptor kinase carboxyl terminus (betaARKCt) is a peptide inhibitor of Gbeta gamma signaling. The central hypothesis is that gene transfer of the betaARKct aortocoronary vein grafts will reduce intimal hyperplasia. Develop and characterize a swine model of intimal hyperplasia in aortocoronary vein grafts. Achieve transgene expression in vein graft smooth muscle cells employing recombinant replication deficient, adenoviral vectors, and study the impact of betaARKct transgene expression on intimal hyperplasia. Study molecular mechanisms of the betaARKct antiproliferative effect on vascular smooth muscle cells in vitro.

静脉移植内膜增生涉及血管平滑肌（VSM）细胞的异常迁移和增殖。最终结果是内膜的增厚，腔体面积减少和血栓闭塞的潜力。该过程限制了反向隐性移植物的有效性作为对冠状动脉狭窄的治疗。 VSM增殖可能取决于涉及GBETA伽马亚基的信号转导。 β-肾上腺素能受体激酶羧基末端（betaarkct）是GBETA伽马信号的肽抑制剂。中心假设是βARKCT主动脉静脉移植物的基因转移将减少内膜增生。开发并表征主动脉静脉移植物中内膜增生的猪模型。采用重组复制缺陷，腺病毒载体的静脉移植平滑肌细胞中的转基因表达，并研究βARKCT转基因表达对内膜增生的影响。研究βARKCT抗增殖作用对血管平滑肌细胞的分子机制。