Balloon injury alters alpha-adrenoceptor expression across rat carotid artery wall.
Balloon injury alters alpha-adrenoceptor expression across rat carotid artery wall.
复制标题
球囊损伤改变大鼠颈动脉壁的α-肾上腺素受体表达。
DOI：
10.1111/j.1440-1681.2006.04347.x
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Yang,Nengyu
中科院分区：
文献类型：
--
作者：
Faber,JamesE;Yang,Nengyu
1a1‐Adrenoceptors (AR) mediate growth factor‐like activity of catecholamines on vascular smooth muscle cells (SMC) and adventitial fibroblasts. This trophic activity is strongly augmented by balloon injury, contributes significantly to subsequent proliferation, wall hypertrophy and lumen loss and is mediated by a1A‐ and a1B‐AR. However, it is not known how injury augments adrenergic trophic activity. The aim of the present study was to examine a‐AR expression in rat carotid artery and to test the hypothesis that balloon injury augments a1‐AR expression.2Neointima, media and adventitia were isolated at various days after balloon injury of rat carotid artery and subjected to quantitative reverse transcription–polymerase chain reaction and radioligand binding. Cultured SMC were also studied.3Transcripts for a1A‐, a1B‐, a1D‐ and a2D‐AR were expressed in different proportions in media and adventitia from uninjured carotid artery. Injury caused a reduction by as much as 85% at day 4 in all a‐AR mRNA (but not cyclophilin) in both the media and adventitia. In both layers, expression returned to control by day 21 for a2D‐AR and by day 42 for a1A‐AR, but remained reduced by 25–50% for a1B‐ and a1D‐AR at 42 days. a1‐Adrenoceptor transcripts in the neointima at 21 and 42 days after injury were expressed at levels more than 80% lower than in the media or adventitia of uninjured carotid; a2D‐AR mRNA was undetectable. The density of total a1‐AR binding sites was similar in the media and adventitia of uninjured carotid. Density was reduced by approximately 60% in the intima–media and adventitia 21 days after injury. To examine possible mechanisms, early passaged cultured SMC were studied that express a1D‐ and a1B‐AR at levels similar toin vivobut that do not express other a‐AR. Basic fibroblast growth factor caused downregulation of a1D‐AR mRNA and a1‐AR density, without affecting mRNA half‐life, whereas transforming growth factor‐b1 had no effect. Neither growth factor altered a1B‐AR message expression.4These data demonstrate that: (i) carotid artery expresses the same four a‐AR genes and similar total a1‐AR density in the SMC media and fibroblast‐rich adventitia; and (ii) injury induced enhancement of adrenergic trophic activity is not caused by upregulation of a1‐AR, but, instead, is associated with a generalized reduction in a‐AR expression.
