血管紧张素-(1-7)在减轻兔腹主动脉球囊损伤后血管壁胶原合成中的作用

Objective To explore the effects of Angiotensin (ANG)-( 1-7 ) on postangioplasty fibrotic remodeling and the involvement of TGF-β/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 μg· kg~(-1) ·d~(-1)) or ANG-(1-7) + A-779 (576 μg · kg~(-1) · 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-β_1 and Stand2 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) μm and (407±25) μm vs. (448 ± 15) μm, P <0. 05, respectively],neointimal area (0.27 ±0.09) mm~2 and (0.38 ±0.01) mm~2 vs. (0.41 ±0.02) mm~2, 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-β_1 , 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-β_1 and inhibiting the activation of Smad2 pathway.

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