Effects of exogenous urotensin II on vascular remodelling after balloon injury.
1. Urotensin II (U-II) is a powerful vasoconstrictor peptide that stimulates cell proliferation. However, the systemic effects of U-II on cellular and extracellular matrix responses of vessel walls have not been investigated. The aim of the present study was to determine the effect of exogenous U-II on arterial neointimal hyperplasia after balloon injury. 2. A stenosis model of the thoracic aorta after balloon injury was established in male Wistar rats. Rats were divided into three groups (n = 5 in each): (i) uninjured; (ii) injured for 21 days; and (iii) injured and then treated with U-II (1 nmol/kg per h) via an osmotic minipump for 21 days. Another group of rats were killed on Days 7 and 14 after balloon injury for the analysis of in vitro collagen synthesis and secretion with U-II treated by [(3)H]-proline incorporation and determination of [(3)H]-hydroxyproline radioactivity, respectively. 3. Urotensin II immunoreactivity was 1.74-fold higher in vessels injured for 21 days than in uninjured vessels and mRNA levels of the urotensin UT receptor were upregulated by 55% following injury. After U-II treatment, the mRNA levels of the UT receptor were further upregulated (by 40%). In addition, U-II treatment increased the intimal area of injured aortas (13 +/- 5 vs 7 +/- 2% in group iii and ii, respectively), as well as increasing collagen content and cell proliferation. Protein levels of matrix metalloproteinase 1 were decreased in U-II-treated rats. In vitro, U-II treatment increased collagen synthesis and secretion in uninjured vessels in a concentration-dependent manner (10(-10), 10(-9) and 10(-8) mol/L U-II), especially in injured aortas on Day 7 after injury. 4. In conclusion, exogenous U-II may upregulate mRNA levels of the UT receptor, as well as increase collagen and cell proliferation, all of which would contribute to intimal hyperplasia after angioplasty.
Zhang
Li-Fang
LF
Division of Cardiology, Department of Internal Medicine, Peking University First Hospital, Beijing, China.
Ding
Wen-Hui
WH
Shi
Li-Bin
LB
Li
Kang
K
Haom
Yan-Jie
YJ
Ke
Yuan-Nan
YN
Tang
Zhao-Shu
ZS
D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D001013:Aorta, Thoracic / Q000293:injuries / Q000473:pathology; D001018:Aortic Diseases; D001020:Aortic Stenosis, Subvalvular; D049109:Cell Proliferation; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D004195:Disease Models, Animal; D006965:Hyperplasia / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D017539:Tunica Intima / Q000293:injuries* / Q000473:pathology / Q000503:physiopathology*; D015854:Up-Regulation; D014579:Urotensins / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D024042:Collagen Type I; D024061:Collagen Type III; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D014579:Urotensins; C473142:Uts2r protein, rat; C029677:urotensin II; D020781:Matrix Metalloproteinase 1