Author + information
- Jingfeng Wang,
- Xue Gong,
- Haiyan Chen and
- Yangang Su
Though cardiac resynchronization therapy(CRT) has now proved to be effective on cardiac reverse remodeling, data on the underlying molecular changes are limited. The present study aims to investigate the expression of cytokines concerning myocardial fibrosis in dyssynchronous heart failure (HF) and the potential benefits of CRT.
Left bundle branch ablation together with rapid pacing was performed to induce a canine model of asynchronous HF. Animals were randomly divided into sham group, HF control group and CRT group. CRT performance lasted for 8 weeks. Echocardiographic data including left ventricular ejection fraction (LVEF), septum-to- posterior wall motion delay (SPWMD) and standard deviation of the time to peak systolic velocity (Ts-SD) were collected. Histologic samples from left ventricular lateral wall were analyzed and compared among different groups. Serum concentrations of NT-proBNP, TGF-β1 and osteopontin (OPN) were measured using ELISA. Protein and mRNA expressions of TGF-β1/Smad and OPN from myocardial tissues were also detected and compared.
Compared with HF control group, animals of CRT group demonstrated improved cardiac function and corrected intraventricular dyssynchrony with increased LVEF(48.6±9.3% vs. 37.0±4.0%, P<0.05), decreased SPWMD (90.8±18.9ms vs. 135.6±26.2ms, P<0.01) and Ts-SD (32.8±4.2ms vs. 41.8±6.9ms, P<0.05). Histological analysis showed that CRT restored cardiomyocyte diameter (from 4.50μm to 6.08μm) and collagen volume fraction (from 19.33% to 11.21%) (P<0.01). Serum concentrations of NT-proBNP (991.6±151.9 pg/ml vs. 1912.6±309.6pg/ml, P<0.01), TGF-β1 (7.4±1.1ng/ml vs. 12.5±2.5ng/ml, P<0.01) and OPN (5.9±1.9ng/ml vs. 8.2±1.6ng/ml, P<0.05) were also significantly decreased after CRT. Compared with sham group, a significantly higher protein and mRNA expressions of TGF-β1/Smad and OPN were observed in HF control group, which were significantly downregulated in CRT group (P<0.01).
By means of coordinating LV dyssynchrony, CRT also invoked cellular and molecular reverse remodeling, which was manifested by myocardial fibrosis inhibition and regulation of TGF-β1/Smad/OPN signaling.