Effect Of Catheter-based Radiofrequency Renal Sympathetic Denervation On Cardiac Fibrosis And MiR-133a/CTGF In Hypertensive Canines

Objective:To evaluate the effect of catheter-based radiofrequency renal sympathetic denervation (RDN) on cardiac fibrosis in hypertensive canine model. Subsidiarily, we investigated the possible mechanism involved by observing cardiac microRNA-133a (miR-133a) and Connective Tissue Growth Factor (CTGF) expression following RDN.Materials and methods:1.28Beagles of age between10-12months were divided into model (n=22) and control group (n=6). Control group was fed with normal diet whereas hypertension model group was fed with high fat diet.2.12weeks after high fat diet feeding, hypertension model group (n=20) was randomized into RDN group (n=10) and Sham group (n=10). Catheter-based renal sympathetic nerve ablation was performed in all animals in RDN group whereas Sham group underwent only renal angiography.3. Animals were weighed and blood pressures were measured at several time points as follow:baseline, pre-procedure, and post-procedure (1,2,4, and6months). Six months post-operatively, all animals were sacrificed and cardiac tissue samples were obtained. The extent of cardiac fibrosis was determined with Masson’s staining by calculating Collagen Volume Fraction (CVF) and Perivascular Collagen Area (PVCA). miR-133a expression was examined with Real-Time PCR. Cardiac CTGF expression was determined with Real-Time PCR and Western Blot.Results:1. Compared to baseline and control group (n=6), body weight, systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) increased significantly in Sham (n=8) and RDN (n=9) groups (P<0.05). No significant differences were found between Sham and RDN groups (P<0.05).2. Compared to pre-operative data and sham group, post-operative SBP, DBP, as well MAP of each time points in RDN group were found marked decreased (P<0.05).3. Compared to control group, Masson’s staining showed cardiac fibrosis in Sham and RDN group. However, CVF and PVCA in RDN group were significantly lower than of those in Sham group (p<0.05).4. Compared to sham group, cardiac miR-133a expression was markedly higher in RDN group while CTGF expression was significantly lower (all p<0.05).Conclusion:1. In hypertensive canine model, RDN effectively improved cardiac fibrosis.2. RDN improved cardiac fibrosis possibly through up-regulating myocardial miR-133a expression which down-regulated CTGF expression.