GW24-e1111 The effects of ACE2 on RAS system by painting on epicadial in atrial rapid pacing canine

Objectives To study the effects of ACE2 on RAS system in rapid atrial pacing canine, and to investigate the possible mechanisms of ACE2 in improving atrial fibrillation "matrix" by inhibiting RAS system. Methods Twenty hybrid dogs were randomly divided into four groups, the sham operation group (Sham group), atrial rapid pacing group (Control group), atrial rapid pacing + ACE2 gene painting group (ACE2 group), atrial rapid pacing + EGFP gene painting group (EGFP group) (n = 5 per group). Electrode under the guidance of right atria ECG fixed in the right atrium through the right external jugular vein, then connected to a custom atrial pacemaker (450 beats/min), and fixed in the dog back. After the placement of pacemaker, Control group were pacing for 3 weeks immediately, and the atria of ACE2 group or EGFP group were painted with mixture solution containing certain concentration of rAd-ACE2 (1*109 pfu/ml) or rAd-EGFP (1*109 pfu/ml), trypsin (0.5%) and Poloxamer F407 (35%) via median sternotomy, then ACE2 group and EGFP group were pacing for 3 weeks. After taking specimens of each group, HE and Sirius red staining were used to observe myocardial interstitial inflammation and fibrosis; Real time PCR was used to analysis mRNA of ACE2, EGFP, AT1 and AT2 receptor; ELISA was used to study the concentration of AngII and Ang (1-7). Results Compared with ACE2 group, there was not the expression of rhACE2 in Sham group, Control group and EGFP group; Ang II level of atrial tissue in Control group was equal with EGFP group, but higher than ACE2 group; Ang (1-7) level in the Control group, EGFP group and Sham group was significantly lower than ACE2 group; HE staining indicated that myocardial interstitial of EGFP and ACE2 group was infiltrated by inflammatory cells significantly of, but inflammatory cells in myocardial interstitial of ACE2 group was slightly less than the EGFP group; Sirius red staining showed that fibrosis level in myocardial interstitial of ACE2 group was significantly lower than EGFP group. Conclusions Exogenous ACE2 gene overexpression in canine atrial tissue can reduce the level of Ang II, transformed into Ang (1-7), and atrial tissue can obtain benefit in the field of anti-inflammatory and anti-fibrotic. Thus, ACE2 could block the activation of the RAS system in atrial rapid pacing canine in certain extent.