G protein signaling and vein graft intimal hyperplasia: reduction of intimal hyperplasia in vein grafts by a Gbetagamma inhibitor suggests a major role of G protein signaling in lesion development.
G protein signaling and vein graft intimal hyperplasia: reduction of intimal hyperplasia in vein grafts by a Gbetagamma inhibitor suggests a major role of G protein signaling in lesion development.
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G 蛋白信号传导和静脉移植物内膜增生：Gbetagamma 抑制剂减少静脉移植物内膜增生，表明 G 蛋白信号传导在病变发展中发挥着重要作用。
DOI：
10.1161/01.atv.18.8.1275
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Koch,WJ
中科院分区：
文献类型：
--
作者：
Davies,MG;Huynh,TT;Fulton,GJ;Lefkowitz,RJ;Svendsen,E;Hagen,PO;Koch,WJ
- 静脉移植导致内膜增生的发展，伴随着鸟嘌呤核苷酸结合（G）蛋白表达和功能的变化。几种通过G蛋白偶联受体（如溶血磷脂酸）发挥作用的血清促分裂素刺激依赖于G蛋白βγ亚基（Gβγ）介导的p21 ras活化的增殖途径。本研究通过在实验性兔静脉移植模型中靶向编码特异性Gβγ抑制剂的基因来检测Gβγ信号在内膜增生中的作用。这种抑制剂是β-肾上腺素能受体激酶（βARKCT）的羧基末端，含有一个Gβγ结合结构域。静脉移植物内膜增生明显减少37%（P<0.01），生理学研究表明，该模型中G蛋白偶联表型的正常改变被β ARKCT治疗所阻断。因此，Gβγ介导的途径似乎在内膜增生中起主要作用，并且靶向Gβγ信号传导抑制剂提供了新的术中治疗方式，以抑制静脉移植物内膜增生和随后的静脉移植物失败的发展。
—Vein grafting results in the development of intimal hyperplasia with accompanying changes in guanine nucleotide–binding (G) protein expression and function. Several serum mitogens that act through G protein–coupled receptors, such as lysophosphatidic acid, stimulate proliferative pathways that are dependent on the G protein βγ subunit (Gβγ)–mediated activation of p21ras. This study examines the role of Gβγsignaling in intimal hyperplasia by targeting a gene encoding a specific Gβγinhibitor in an experimental rabbit vein graft model. This inhibitor, the carboxyl terminus of the β-adrenergic receptor kinase (βARKCT), contains a Gβγ-binding domain. Vein graft intimal hyperplasia was significantly reduced by 37% (P<0.01), and physiological studies demonstrated that the normal alterations in G protein coupling phenotypically seen in this model were blocked by βARKCTtreatment. Thus, it appears that Gβγ-mediated pathways play a major role in intimal hyperplasia and that targeting inhibitors of Gβγsignaling offers novel intraoperative therapeutic modalities to inhibit the development of vein graft intimal hyperplasia and subsequent vein graft failure.
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影响因子：
37.8
作者：
Yi Shi;A. Fard;Anthony Galeo;H. Hutchinson;Pawan Vermani;G. R. Dodge;D. Hall;F. Shaheen;A. Zalewski
通讯作者：
A. Zalewski
DOI：
10.1016/s0021-9258(17)37587-7
发表时间：
1994-02
期刊：
The Journal of biological chemistry
影响因子：
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作者：
W. Koch;B. Hawes;James Inglese;L. Luttrell;R. Lefkowitz
通讯作者：
W. Koch;B. Hawes;James Inglese;L. Luttrell;R. Lefkowitz
DOI：
10.1073/pnas.92.10.4502
发表时间：
1995-05-09
影响因子：
11.1
作者：
MANN, MJ;GIBBONS, GH;DZAU, VJ
通讯作者：
DZAU, VJ
影响因子：
56.9
作者：
PITCHER, JA;INGLESE, J;LEFKOWITZ, RJ
通讯作者：
LEFKOWITZ, RJ
DOI：
10.1073/pnas.91.26.12706
发表时间：
1994-12-20
影响因子：
11.1
作者：
KOCH, WJ;HAWES, BE;LEFKOWITZ, RJ
通讯作者：
LEFKOWITZ, RJ