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[Angiotensin-(1-7) reduced postangioplasty vascular fibrosis in abdominal aorta of rabbits].
- Source :
-
Zhonghua xin xue guan bing za zhi [Zhonghua Xin Xue Guan Bing Za Zhi] 2010 Jun; Vol. 38 (6), pp. 531-8. - Publication Year :
- 2010
-
Abstract
- Objective: To explore the effects of Angiotensin (ANG)-(1-7) on postangioplasty fibrotic remodeling and the involvement of TGF-beta/Smad signaling pathway in this process.<br />Methods: Thirty two healthy New Zealand white rabbits were randomly divided into 4 groups: sham group, control group, ANG-(1-7) group and ANG-(1-7) + A-779 group. Rabbits underwent angioplasty in the abdominal aorta or sham surgery. Subsequently, an osmotic minipump was implanted for saline, ANG-(1-7) (576 microg x kg(-1) x d(-1)) or ANG-(1-7) + A-779 (576 microg x kg(-1) x d(-1)) delivery. Before and after 4 weeks treatment, the levels of ANG II in plasma were measured by ELISA. At week 4, angiography and histomorphometric analysis were performed, mRNA levels of collagen I and III were assayed by RT-PCR and protein levels of TGF-beta1 and Smad2 in local vessel were assayed by Western blot.<br />Results: Following 4 weeks treatment, ANG-(1-7) and ANG-(1-7) + A-779 group displayed a significant elevation in lumen diameter [(4.11 +/- 0.10) mm and (3.34 +/- 0.11) mm vs. (2.88 +/- 0.08) mm, P < 0.05, respectively] and reduction in neointimal thickness [(208 +/- 17) microm and (407 +/- 25) microm vs. (448 +/- 15) microm, P < 0.05, respectively], neointimal area [(0.27 +/- 0.09) mm2 and (0.38 +/- 0.01) mm2 vs. (0.41 +/- 0.02) mm2, P < 0.05, respectively] and restenosis rate [(28.1 +/- 2.7)% and (36.8 +/- 2.2)% vs. (40.1 +/- 2.7)%, P < 0.05, respectively] compared with control group. Collagen I, III mRNA and TGF-beta1, Smad2 protein levels were significantly elevated in control group, ANG-(1-7) group and ANG-(1-7) +A-779 group compared to sham group (P < 0.01 or P < 0.05) and reduced in ANG-(1-7) group compared to control group (all P < 0.05). Co-treatment with A-779 reversed the inhibitory action of ANG-(1-7). Plasma levels of ANG II postangioplasty were similar in control and ANG-(1-7) group and both were significantly higher than preoperation levels.<br />Conclusion: ANG-(1-7) attenuates postangioplasty collagen synthesis in rabbits possibly through down-regulating the expression of TGF-beta1 and inhibiting the activation of Smad2 pathway.
- Subjects :
- Animals
Aorta, Abdominal metabolism
Aorta, Abdominal pathology
Collagen Type I metabolism
Collagen Type III metabolism
Rabbits
Signal Transduction
Smad2 Protein metabolism
Transforming Growth Factor beta1 metabolism
Angiotensin I pharmacology
Aorta, Abdominal drug effects
Fibrosis metabolism
Muscle, Smooth, Vascular metabolism
Peptide Fragments pharmacology
Subjects
Details
- Language :
- Chinese
- ISSN :
- 0253-3758
- Volume :
- 38
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Zhonghua xin xue guan bing za zhi
- Publication Type :
- Academic Journal
- Accession number :
- 21033136