Norepinephrine reversibly regulates the proliferation and phenotypic transformation of vascular smooth muscle cells.
OBJECTIVE
To investigate the effect of norepinephrine (NE) on the proliferation and phenotypic transformation of vascular smooth muscle cells (VSMCs) and the mechanisms underlying this effect.


METHODS
VSMCs 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), alpha-adrenergic receptor agonist (alpha1-R(-)), beta1-adrenergic receptor antagonist (beta1-R(-)) and various combinations of these factors. VSMC proliferation was determined by bromodeoxyuridine (BrdU) assays. The mRNA expression level of HRG-1 and SM22 alpha were determined by reverse transcription-polymerase chain reaction (RT-PCR).


RESULTS
The expressions of HRG-1 and SM22 alpha mRNA in NE- or OX-LDL-treated VSMCs was down-regulated, and the proliferation of BrdU-labeled cells increased; the expression of the above mentioned genes in the VSMCs treated with a combination of NE, alpha1-R, and beta1-R was significantly up-regulated. However, NE was observed to up-regulate the expression of HRG-1 and SM22 alpha mRNA in serum-starved VSMCs.


CONCLUSIONS
NE could reversibly regulate the proliferation and phenotypic transformation of VSMCs. This regulation might be mediated via its receptors.
Jiao
Lei
L
Department of First Clinical Hospital, Medical College, Suzhou University, Suzhou 215123, China.
Wang
Min-Chen
MC
Yang
Ya-An
YA
Chen
Er-Qi
EQ
Xu
Hong-Tao
HT
Wu
Kai-Yun
KY
Zhang
Shi-Ming
SM
D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002461:Cell Line, Transformed; D049109:Cell Proliferation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D007150:Immunohistochemistry; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D020890:Neuregulin-1 / Q000235:genetics / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology*; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044967:Serum
D008840:Microfilament Proteins; D009124:Muscle Proteins; D020890:Neuregulin-1; D012333:RNA, Messenger; C051615:transgelin; D001973:Bromodeoxyuridine; D009638:Norepinephrine