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Effects of exogenous urotensin II on vascular remodelling after balloon injury
Author(s) -
Zhang LiFang,
Ding WenHui,
Shi LiBin,
Li Kang,
Haom YanJie,
Ke YuanNan,
Tang ZhaoShu
Publication year - 2010
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2009.05336.x
Subject(s) - urotensin ii , hydroxyproline , intimal hyperplasia , endocrinology , medicine , receptor , downregulation and upregulation , neointima , chemistry , restenosis , biochemistry , stent , smooth muscle , gene
Summary 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.