Inhibitory effect of angiotensin II type 1 receptor-associated protein on vascular smooth muscle cell growth and neointimal formation.
OBJECTIVE
To investigate the mechanism of a novel angiotensin II type 1 receptor-associated protein (ATRAP) interfering with angiotensin II type 1 (AT1) receptor-mediated vascular smooth muscle cell (VSMC) growth and neointimal formation.


METHODS
VSMCs isolated from thoracic aorta of adult Sprague-Dawley (SD) rats were used in this study. ATRAP cDNA was subcloned into pcDNA3 vector and then transfected into VSMCs. DNA synthesis and extracellular signal-regulated kinase (ERK) and phospho-ERK expressions in VSMCs were assayed by measurement of 3H thymidine incorporation and Western blotting, respectively. Morphological changes were observed in the balloon injured artery with or without transfection of ATRAP cDNA using 12-week-old male SD rats.


RESULTS
ATRAP overexpression in VSMCs inhibited angiotensin II (Ang II)-induced 3H thymidine incorporation 48 hours after Ang II stimulation (P < 0.05). In VSMC, Ang II stimulation increased the phosphorylation of ERK, which reached the peak around 60 minutes. The activation of phospho-ERK was significantly decreased by ATRAP (P < 0.05). Neointimal formation was markedly inhibited by ATRAP overexpression in injuried arteries.


CONCLUSIONS
The AT1 receptor-derived activation of ERK plays an essential role in Ang II-induced VSMC growth. The growth inhibitory effects of ATRAP might be due to interfering with AT1 receptor-mediated activation of ERK in VSMC growth and neointimal formation.
Li
Zhen
Z
Department of Vascular Surgery, Second Artillery General Hospital, Beijing 100088. zhenli0328@hotmail.com
Wang
Zhong-Gao
ZG
Chen
Xiu
X
Chen
Xiao-Dong
XD
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology*; D002455:Cell Division; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000502:physiology*; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology; D011945:Receptors, Angiotensin / Q000235:genetics / Q000502:physiology*; D014162:Transfection; D017539:Tunica Intima / Q000166:cytology*
C524087:Agtrap protein, rat; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D048049:Extracellular Signal-Regulated MAP Kinases