Hypertension is associated with inflammation, increased cytokine concentrations and exacerbated immune responses. Increased levels of angiotensin II contribute to intensify the effects of the complement system, C3a and C5a, in their receptors. The activation of the complement system decreases the levels of Foxp3 and inhibits the immunosuppressive actions of regulatory T cells in vivo. Furthermore, increased levels of C3a contributes to trigger oxidative stress and increase the expression of matrix metalloproteinase (MMP)-2 in the aortas of an aneurysm model, an important protease that contributes to arterial remodeling in many cardiovascular diseases. We analyzed whether increased C3a levels contributes to trigger oxidative stress and MMP-2 activation in mice aortas, thus contributing to vascular remodeling and dysfunction in hypertension. C57BL/6 mice were submitted to a surgery where minipumps containing either angiotensin II 1mg/kg/day or vehicle were subcutaneously implanted. Mice were also treated with the C3aR antagonist (SB290157), at 1mg/kg/day intraperitoneally, every other day for 14 days (CEUA-USP 122/2019). Tail-cuff plethysmography was done every two days after minipumps implantation for measuring systolic blood pressure (SBP). The aortas were collected to analyze MMP-2 activity by gel and in situ zymography and oxidative stress production by immunofluorescence of DHE. Statistics were performed by two- or one-way ANOVA followed by Tukey's post-test. p<0.05 was used. The SBP was higher in the angiotensin II mice compared to Sham and Sham+antagonist (143.5±4.7 vs. 104.8±2.4 and 114.3±4.6; p<0.05; n=7). Treatment with the antagonist of C3a notably decreased it (118.0±4.7; p<0.05; n=8). By in situ and gel zymography, MMP-2 activity was increased in the aortas of angiotensin II mice (vs. controls; p<0.05; n=5) and the antagonist was able to decrease it (p<0.05; n=5). Lastly, the production of oxidative stress was also evaluated in the aortas by DHE. There was an increase in the production of oxidative stress in the aortas of hypertensive mice and the antagonist significantly reduced it (57.4±2.7 vs. 39.4±3.4; p<0.05; n=5). In conclusion, treatment with the antagonist of C3aR reduced the accentuated SBP in angiotensin II mice in addition to reduce oxidative stress and MMP-2 activity in the aortas. We are next evaluating whether these mechanisms contribute to cause vascular remodeling and dysfunction in hypertension.
Comissão Organizadora
Gustavo Carvalho
Luiza Malacco
Eliana Hiromi Akamine
Profª Drª Luciana Venturini Rossoni
Ana Paula Couto Davel
José Wilson do Nascimento Corrêa
GIULIA ALESSANDRA WIGGERS
Alice Valença Araújo
Comissão Científica
Ferramenta completa de submissão, avaliação e publicação de anais para eventos científicos.
