The Effects Of ACE2on RAS System By Painting On Epicadial Inatrial Rapid Pacing Canine

Objective: To study the effects of ACE2on RAS system in rapid atrialpacing canine, and to investigate the the possible mechanism of ACE2inimproving "matrix" of atrial fibrillation by inhibiting RAS system.Method: For this study，twenty hybrid dogs were randomlydivided intothe EGFPgene painting group (Shamgroup，n=5), atrialrapid pacing group(Control group，n=5), atrial rapid pacing+ACE2gene painting group（ACE2group，n=5）, atrial rapid pacing+EGFP gene painting group(EGFPgroup，n=5).Electrode under the guidance ofright atria ECG fixed inthe right atrium through the right external jugular vein, then connected to acustom atrial pacemaker (450beats/min), and fixed it on dog back. Afterthe placement of pacemaker，the dog in Control group was pacing for3weeks immediately，and the atria of experimental dog inACE2group （orEGFP group） were painted with mixture solution containing certainconcentration of rhAd-ACE2（1*109pfu/ml）（orrAd-EGFP(1*109pfu/ml)）, trypsin（0.5%）and Poloxamer F407（35%）via median sternotomy, then pacing was performed both in ACE2andEGFP group. After taking specimens of each group, HE and Sirius red staining were used to observe myocardial interstitial inflammation andfibrosis; Real time PCR was used to analysis mRNA expression ofACE2,EGFP,AT1-R and AT2-R; Immunohistochemical staining andImage-Pro Plus analysis were used to study the expression level of AngⅡand Ang（1-7）.Result：Compared with ACE2group, there was no expression ofrh-ACE2in Sham group, Control group and EGFP group; Ang IIexpression level of atrial tissue in Control group was higher than that inSham group，but was similar to ACE2group; Ang II level of atrial tissue inACE2was lower thanthat in EGFPgroup；Ang(1-7) levelofatrialtissue inACE2group was higher thanthat in EGFPgroup，Control group and Shamgroup; HE staining indicated that myocardial interstitial of EGFP and ACE2group were infiltrated by inflammatorycells significantly; Sirius red stainingshowed that fibrosis level in myocardial interstitial of ACE2group wassignificantly lower than that in EGFP group.Conclusion：ACE2gene overexpression in canine atrial tissue canreduce the level of Ang II, transformed it into Ang (1-7), and atrial tissue canobtain benefit in the field of anti-fibrotic.Thus, ACE2may block theactivation of the RAS system in atrial rapid pacing canine.