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Chronic angiotensin-(1-7) administration improves vascular remodeling after angioplasty through the regulation of the TGF-beta/Smad signaling pathway in rabbits.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2009 Nov 06; Vol. 389 (1), pp. 138-44. Date of Electronic Publication: 2009 Aug 26. - Publication Year :
- 2009
-
Abstract
- Objective: Angiotensin-(1-7) [ANG-(1-7)] has been reported to attenuate neointimal formation after vascular injury and stent implantation in rats, but the mechanism remains mostly unresolved. Interestingly, the levels of circulating transforming growth factor-beta1 (TGF-beta1) after myocardial infarction were suppressed by ANG-(1-7), which suggests a possible downstream target for the anti-remodeling action of ANG-(1-7). Our study focused on the effects of ANG-(1-7) on vascular remodeling, including neointimal formation and collagen synthesis, and determining whether or not these effects were dependent upon the TGF-beta signaling pathway.<br />Methods: Thirty-two New Zealand white rabbits underwent sham surgery or angioplasty in abdominal aorta. The animals were divided into four groups, which were sham, control, ANG-(1-7), and ANG-(1-7)+A-779. Subsequently, an osmotic minipump was implanted to deliver saline, ANG-(1-7) (576 microg kg(-1)d(-1)) or ANG-(1-7)+A-779 (576 microg kg(-1)d(-1)) for 4 weeks.<br />Results: The ANG-(1-7) group displayed a significant reduction in neointimal thickness (207.51+/-16.70 microm vs. 448.08+/-15.30 microm, P<0.001), neointimal area (0.266+/-0.009 mm(2) vs. 0.408+/-0.002 mm(2), P<0.001), and restenosis rate (28.13+/-2.74% vs. 40.13+/-2.74%, P<0.001) when compared to the control group. ANG-(1-7) also inhibited collagen synthesis by significantly decreasing the mRNA expression of Collagen I and Collagen III (vs.<br />Control Group: 0.2190+/-0.0036 vs. 0.3852+/-0.0212, P<0.001 and 1.1328+/-0.0554 vs. 1.7378+/-0.1164, P<0.001, respectively). Furthermore, the expression of TGF-beta1 and phosphor-Smad2 (p-Smad2) were significantly suppressed by ANG-(1-7) (vs.<br />Control Group: 1.21+/-0.07 vs. 1.54+/-0.08, P<0.001 and 0.31+/-0.01 vs. 0.43+/-0.02, P<0.001, respectively), but no effect on p38 phosphorylation was observed. [d-Ala(7)]-ANG-(1-7) (A-779), showed a tendency to attenuate the anti-remodeling effects of ANG-(1-7).<br />Conclusion: ANG-(1-7) decreases the amount of vascular remodeling, including a reduction in neointimal formation and collagen synthesis, after angioplasty in rabbits. The responsible mechanism may function through the possible down-regulation of TGF-beta1 levels and inhibition of the Smad2 pathway.
- Subjects :
- Angioplasty
Animals
Aorta, Abdominal physiology
Blood Pressure drug effects
Collagen Type I biosynthesis
Collagen Type III biosynthesis
Heart Rate drug effects
Rabbits
Rats
Smad2 Protein antagonists & inhibitors
Transforming Growth Factor beta antagonists & inhibitors
Tunica Intima physiology
Tunica Intima surgery
Aorta, Abdominal drug effects
Aorta, Abdominal surgery
Regeneration drug effects
Smad2 Protein metabolism
Transforming Growth Factor beta metabolism
Tunica Intima drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2104
- Volume :
- 389
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 19715669
- Full Text :
- https://doi.org/10.1016/j.bbrc.2009.08.112