Enhanced vasorelaxation by overexpression of beta 2-adrenergic receptors in large arteries.
Enhanced vasorelaxation by overexpression of beta 2-adrenergic receptors in large arteries.
复制标题
通过大动脉中β2-肾上腺素能受体的过度表达增强血管舒张作用。
DOI：
10.1006/jmcc.1998.0668
复制
发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Goldman,S
中科院分区：
文献类型：
--
作者：
Gaballa,MA;Peppel,K;Lefkowitz,RJ;Aguirre,M;Dolber,PC;Pennock,GD;Koch,WJ;Goldman,S
本研究旨在确定腺病毒介导的编码β2-肾上腺素能受体（β2-AR）的转基因递送到颈动脉壁是否会导致体内血管功能的改变。用0.1mg/ml弹性蛋白酶和腺病毒[6× 109个空斑形成单位（PFU）]灌注去内皮化大鼠颈动脉，腺病毒含有标记基因β-半乳糖苷酶（Adeno-β-gal）、编码人β2-AR的DNA（Adeno-β2-AR）或不含转基因。这种低浓度的弹性蛋白酶增加了水的渗透性（5.2±0.6v1.9±0.4×10− 8 cm/s/mmHg，n=4，P<0.0001），而不影响血管反应性或动脉壁的形态。Adeno-β-gal（n=3）的转染效率为73%，β-gal的表达与T、B淋巴细胞或中性粒细胞浸润的少见出现有关。Adeno-β2-AR感染后5天，总β-AR密度增加6倍（67.8±3.4v397.0±155.5 fmol/mg蛋白，n=5，P<0.01）;在10-110 mmHg的跨壁压下，异丙肾上腺素诱导的血管舒张增加与暴露于对照病毒（空腺病毒）的动脉相比，（P<0.01），n=4;并且异丙肾上腺素刺激的cAMP产生增加了65%（n=5）。因此，腺病毒介导的β2-AR向大动脉壁的递送通过血管平滑肌细胞中cAMP水平的增加导致β-AR介导的血管舒张增强。
This study was designed to determine if adenoviral-mediated delivery of a transgene encoding theβ2-adrenergic receptor (β2-AR) to the carotid arterial wall could result in alterations inin vivovascular function. De-endothelialized rat carotid arteries were infusedin vivowith 0.1 mg/ml elastase and adenovirus [6×109plaque forming units (PFU)] containing either the marker geneβ-galactosidase (Adeno-β-gal), DNA encoding the humanβ2-AR (Adeno-β2-AR), or no transgene. This low concentration of elastase increased the water permeability (5.2±0.6v1.9±0.4×10−8cm/s/mmHg,n=4,P<0.0001) without affecting either the vasomotor responsiveness or the morphology of the arterial wall. A transfection efficiency of 73% was achieved with Adeno-β-gal (n=3).β-gal expression was associated with infrequent appearance of T and B lymphocytes, or neutrophil infiltration. Five days after infection with Adeno-β2-AR, the totalβ-AR density increased six-fold (67.8±3.4v397.0±155.5 fmol/mg protein,n=5,P<0.01); isoproterenol-induced vasorelaxation at transmural pressures from 10–110 mmHg increased (P<0.01) compared to arteries exposed to control virus (empty adenovirus),n=4; and isoproterenol-stimulated cAMP production was increased by 65% (n=5). Thus, adenoviral-mediated delivery ofβ2-ARs into large artery walls results in enhancedβ-AR-mediated vasorelaxation via augmentation in cAMP levels in vascular smooth muscle cells.