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AB0086 Preventive effects of angiotensin 1-7 on neoangiogenesis and leukocyte trafficking increase in the early phases of an experimental model of antigen induced arthritis
  1. F Fischetti,
  2. P Durigutto,
  3. D De Nardo,
  4. R Carretta
  1. University of Trieste Italy, Trieste, Italy

Abstract

Background Renin Angiotensin System (RAS) might be supposed to be involved in the early and late phases of development of synovitis, since data exist showing that Angiotensin (AT)-II contributes to the development of vascular damage under early inflammatory conditions (1, 2). Little is known about AT 1–7 functions, which is supposed to play counteracting actions vs AT II, under these conditions (2, 3)

Objectives to evaluate if, in the early phases of an experimental model of arthritis, namely the antigen-induced arthritis (AIA), treatment with AT 1–7 could interfere with the synovial development of capillary vascular growth, and prevent leukocyte trafficking activation, in vivo, either at synovial and at mesentery post-capillary venules.

Methods in compliance with European (86/609/EEC) and the Italian (D.L.116/92) ethics committees, 2 groups each of 8 male (240–270 gr) Wistar rats were randomly chosen and treated respectively with sterile saline, or with AT 1–7 (576 μg/kg/day), during the time of immunization with methylated serum bovine albumin (mBSA). Arthritis was induced by intraarticular administration of mBSA (0.1mg in 100ml sterile saline) into the right knee of each animal, after previous immunization to mBSA emulsified in complete Freund's adjuvant. The left knee, injected with only saline, served as a control. Two and 5 days after arthritis induction, the count of capillary branches, and the number of fluorescently-labelled leukocytes, showing transient or stable adhesion to the endothelial microvascular layer (EL), were assessed by using an in vivo videomicroscopy technique.

Results synovial branching vessels with diameter >20μm were not modified after AIA induction, while microvessels having diameter less than 20 μm were significantly increased. After 2 and 5 days, AT 1–7 reduced the number of neo expressed <20μm diameter vessels (Day2: 3.7±3.4 vs 7.7±5.05, p=ns; Day5: 12.7±6.9 vs 21.0±7.3, p<0.05; both significantly greater than control joints). Transient and stable adhesion to EL showed to be partially reduced 2 days after AIA induction and significantly reduced after 5 days (Day5, transient=12.5±6.2 vs 26.0±9.0, p<0.05; stable=27.0±8.3 vs 41.7±10.6, p<0.05; both significantly greater than control joints). Comparable results were found when analysing the number of leukocytes adhering to mesentery EL.

Conclusions we suggest that AT 1–7 could play an immune modulating role in the early phase of synovitis with possible prevention of further inflammatory and secondary structural tissue alterations. These data further support the hypothesis that mechanisms leading to synovial AT-II activation have a detrimental role in the development of arthritis.

References

  1. Candido R, et al. Circulation 2004;109:1536–1542.

  2. Zhang F et al, Sci Rep. 2016; 6: 34621.

  3. Villalobos LA et al, Front Pharmacol. 2016; 7: 482.

References

Disclosure of Interest None declared

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