Gene expression profiles in response to the activation of adrenoceptors in A7R5 aortic smooth muscle cells

Yongyu Wang, Rong Hou, Ping Li, Jinliang Li, Jie Yan, Feng Yin, Chide Han, Youyi Zhang

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

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 α1- or β-adrenoceptors, a DNA microarray was used. 2. First, the existence of α1- and β-adrenoceptors in A7r5 aortic smooth muscle cells was confirmed by radioligand binding. Then, the inhibitory effects of phenylephrine (an α1-adrenoceptor agonist) and isoproterenol (a β-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 α1-adrenoceptors was very different from that following activation of β-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 α1-adrenoceptors (with phenylephrine) and β-adrenoceptors (with isoproterenol) inhibited the proliferation of A7r5 cells, but microarray data revealed that the mechanisms may be different: the activation of α1-adrenoceptors could induce the expression of metabolic genes, resulting in the inhibition of proliferation, whereas activation of β-adrenoceptors altered the expression of genes that encoded cell signalling and structure proteins to inhibit cell proliferation.

Original languageEnglish (US)
Pages (from-to)602-607
Number of pages6
JournalClinical and Experimental Pharmacology and Physiology
Volume31
Issue number9
DOIs
StatePublished - Sep 1 2004

Keywords

  • Adrenoceptors
  • DNA microarray
  • Gene expression profile
  • Proliferation
  • Vascular smooth muscle cells

ASJC Scopus subject areas

  • Physiology
  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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