IngentaConnect Gene expression profiles in response to the activation of adrenoc...

Abstract:

Summary

1. Vascular adrenoceptors play an important role in vascular physiology and pathophysiology, such as hypertension, atherosclerosis and restenosis after angioplasty. To define the changes in the ene expression in vascular smooth muscle cells in response to the activation of agr

₁- or

-adrenoceptors, a DNA microarray was used.

2. First, the existence of agr

₁- and

-adrenoceptors in A7r5 aortic smooth muscle cells was confirmed by radioligand binding. Then, the inhibitory effects of phenylephrine (an agr

₁-adrenoceptor agonist) and isoproterenol (a bgr

-adrenoceptor agonist) on the proliferation of A7r5 cells were determined by [³H]-thymidine incorporation.

3. The A7r5 cells were treated with 10 µmol/L phenylephrine or 1 µmol/L isoproterenol for 24 h and changes in gene expression were detected with the DNA microarray. Only 14 and 20 genes were identified after treatment of cells with phenylephrine and isoproterenol, respectively, and most genes displayed decreased expression. The changed genes could be grouped into five major functional categories: cell signalling/communication, cell structure/motility, cell/organism defence, gene/protein expression and metabolism. The gene expression profile in response to the activation of agr

₁-adrenoceptors was very different from that following activation of bgr

-adrenoceptors. Interestingly, many phenylephrine-responsive genes were associated with metabolism, whereas many isoproterenol-responsive genes encoded cell signalling and structure proteins. This means that adrenoceptors may modulate multiple aspects of biological function in vascular smooth muscle cells.

4. Collectively, the activation of both agr

₁-adrenoceptors (with phenylephrine) and bgr

-adrenoceptors (with isoproterenol) inhibited the proliferation of A7r5 cells, but microarray data revealed that the mechanisms may be different: the activation of agr

₁-adrenoceptors could induce the expression of metabolic genes, resulting in the inhibition of proliferation, whereas activation of bgr

-adrenoceptors altered the expression of genes that encoded cell signalling and structure proteins to inhibit cell proliferation.

Keywords: adrenoceptors; DNA microarray; gene expression profile; proliferation; vascular smooth muscle cells

Document Type: Research article

DOI: 10.1111/j.1440-1681.2004.04058.x

Affiliations: 1: Institute of Vascular Medicine, Peking University Third Hospital and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing, PR China

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Gene expression profiles in response to the activation of adrenoceptors in A7r5 aortic smooth muscle cells