[Angiotensin-(1-7) reduced postangioplasty vascular fibrosis in abdominal aorta of rabbits].

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.

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.

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.

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.

• Authors: Wu-tao Zeng, Wei-yan Chen, Xiu-yu Leng, Jian-gui He, Hong Ma
• Journal: Zhonghua xin xue guan bing za zhi (Zhonghua Xin Xue Guan Bing Za Zhi) Vol. 38 Issue 6 Pg. 531-8 (Jun 2010) ISSN: 0253-3758 [Print] China
• PMID: 21033136 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Collagen Type I
• Collagen Type III
• Peptide Fragments
• Smad2 Protein
• Transforming Growth Factor beta1
• Angiotensin I
• angiotensin I (1-7)

Topics

• Angiotensin I (pharmacology)
• Animals
• Aorta, Abdominal (drug effects, metabolism, pathology)
• Collagen Type I (metabolism)
• Collagen Type III (metabolism)
• Fibrosis (metabolism)
• Muscle, Smooth, Vascular (metabolism)
• Peptide Fragments (pharmacology)
• Rabbits
• Signal Transduction
• Smad2 Protein (metabolism)
• Transforming Growth Factor beta1 (metabolism)