The Influence of BDNF and Exercise on the Progression of Heart Failure in Mice

Abstract

IntroductionRecent studies suggest that not only exercise training but also brain‐derived neurotrophic factor (BDNF) influences the progression of heart failure (HF). While HF patients exhibit low BDNF levels, higher serum BDNF is associated with a decreased risk for HF. This study analyzed the influence of BDNF alone and in combination with exercise training, on the cardiac function of transgenic αMHC‐Gαq mice suffering from HF.MethodsFive week old αMHC‐Gαq mice (n=22) were randomized into four groups: control (CON; n=9), exercise (EX; n=5), BDNF (BDNF; n=5) and exercise in combination with BDNF (EX+BDNF; n=3). BDNF and EX+BDNF mice received weekly intraperitoneal BDNF injections (0.05 μg/g bodyweight). CON and EX received NaCl (100 μl/injection). Cardiac structure and function was assessed weekly using echocardiography under isoflurane anesthesia starting on day 0 (baseline [BL]) and ending on day 49 (week 7 [WK7]). Animals in the EX and the EX+BDNF group had access to a running wheel (voluntary running). An ANOVA with fixed effects for time and group as well as for the corresponding interaction was used to assess the impact of BDNF and exercise on left ventricular structure and function.ResultsIn BDNF treated mice end‐diastolic diameters (EDD) (9.0%; 95%‐CI: −1.19% to 18.1%; p = .04) and end‐diastolic volume (EDV) (23.4%; 95% CI: −0.5% to 47.2%; p = .03) significantly increased from BL to WK7. Furthermore, BDNF treated mice had larger end‐systolic volumes (50.0%; 95%‐CI: −18.71% to 118.7%; p = .05). EDD (13.3%; CI: −11.48% to 38.1%; p = .04) and EDV (36.0%; CI: −32.2% to 104.3%; p = .04) increased in the BDNF+EX group. Additionally, BDNF+EX as well as EX mice showed a diastolic thickening of the left anterior wall (LVAW, d) of 63.1% (95%‐CI: 62.6% to 63.5%; p = .03) and (43.7%; 95%‐CI: 26.5% to 65.0%; p < .01), respectively. We identified a significant group and time interaction for left ventricular mass (p = .01). This was exemplified by an increase of 22.0% (95%‐CI: 7.50% to 36.5%; p = .03) in CON, 28.6% (95%‐CI: −24.04% to 61.2%; p = .02) in BDNF, 52.3% (95%‐CI: 28.9% to 75.8%; p < .01) in EX and 47.60% (95%‐CI: 82.14% to 177.4%; p < .01) in EX+BDNF. Diastolic function assessed by E/e’ was not affected by BDNF or exercise.ConclusionOur results demonstrate that animals who received BDNF showed increased EDD and EDV diameters independent of exercise training. Exercise training resulted in a larger increase in left ventricular mass and LVAW, d compared to the sedentary animals independent of BDNF treatment. Further research is warranted to understand the interaction between BDNF and exercise on HF progression and its potential clinical application. Our results as of now are inconclusive regarding the potential cardio‐protective effects of BDNF.Support or Funding InformationGerman Center for Cardiovascular Research (DZHK)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.