Alteration of vascular urotensin II receptor in mice with apolipoprotein E gene knockout.
Urotensin II (U-II), originally identified as a fish neuropeptide, exerts a broad spectrum of biological functions and is considered to be the most potent vasoconstrictor in mammals. Recently the intense staining of U-II-like immunoreactivity within coronary atheroma and the effect of mitogenic in vascular smooth muscle cells (VSMCs) suggest that U-II is possibly a proatherogenic factor in the pathogenesis of cardiovascular diseases (CVD). In the present study, we analyzed the gene expression of U-II and GPR14, a high-affinity receptor for U-II, in aorta of apolipoprotein E (apoE) -/- mutant mice by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). Compared with wild-type mice at the same age group, GPR14 mRNA level is significant increase in aorta of apoE -/- mice at age of 18, 28 and 38 weeks, respectively. The increased GPR14 mRNA level was 54.2, 50.0 and 97.0% in the three age groups, respectively. We did not detect U-II mRNA expression in aorta either in apoE -/- mice or in wild-type mice. In 28-week mice, ligand-binding assay showed that maximum binding capacity (Bmax) of 125I-U-II aorta from apoE -/- mice was increased by 64%, while the affinity of the binding did not change compared with that of wild-type mice. These results indicate that the up-regulation of vascular U-II receptor (UT), GPR14 might be involved in the pathogenesis of atherosclerosis.
Wang
Zhi Jian
ZJ
Division of Cardiology, Department of Internal Medicine, Peking University First Hospital, Xishikudajie #8, West District, Beijing 10034, China.
Shi
Li Bin
LB
Xiong
Zhuo Wei
ZW
Zhang
Li Fang
LF
Meng
Lei
L
Bu
Ding Fang
DF
Tang
Chao Shu
CS
Ding
Wen Hui
WH
D000367:Age Factors; D000818:Animals; D001011:Aorta; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics*; D017353:Gene Deletion; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D014579:Urotensins / Q000378:metabolism*
D001057:Apolipoproteins E; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D014579:Urotensins; C512325:urotensin II receptor, mouse; C029677:urotensin II