Norepinephrine reversibly regulates the proliferation and phenotypic transformation of vascular smooth muscle cells

ObjectiveTo investigate the effect of norepinephrine (NE) on the proliferation and phenotypic transformation of vascular smooth muscle cells (VSMCs) and the mechanisms underlying this effect.MethodsVSMCs were isolated from the rat abdominal aorta. VSMCs cultured in both serum-containing or in a serum-free medium were treated with NE, oxidized low-density lipoprotein (ox-LDL), α-adrenergic receptor agonist (α1-R−), β1-adrenergic receptor antagonist (β1-R−) and various combinations of these factors. VSMC proliferation was determined by bromodeoxyuridine (BrdU) assays. The mRNA expression level of HRG-1 and SM22α were determined by reverse transcription-polymerase chain reaction (RT-PCR).ResultsThe expressions of HRG-1 and SM22α mRNA in NE- or OX-LDL-treated VSMCs was down-regulated, and the proliferation of BrdU-labeled cells increased; the expression of the abovementioned genes in the VSMCs treated with a combination of NE, α1-R, and β1-R was significantly up-regulated. However, NE was observed to up-regulate the expression of HRG-1 and SM22α mRNA in serum-starved VSMCs.ConclusionNE could reversibly regulate the proliferation and phenotypic transformation of VSMCs. This regulation might be mediated via its receptors.