Endurance Exercise Training Prevents Elevation of Soluble ST2 in Mice with Doxorubicin-Induced Myocardial Injury.

Abstract

Background and objectives: Endurance exercise training (ET) can improve outcomes for patients with heart failure (HF). We investigated the preventive effects of ET on serum biomarkers for HF in mice treated with doxorubicin (DOX).

Methods: A cohort of male wild-type mice were randomly assigned to 3 groups: sedentary control (CON), DOX-treated sedentary (DOX), and DOX-treated endurance ET (ET-DOX) groups. ET groups performed moderate intensity endurance ET on a motor treadmill for 8 weeks. After 8 weeks, the DOX and ET-DOX groups were treated with DOX via weekly intraperitoneal injections of 8 mg/kg for a total of 4 weeks. We compared M-mode echocardiography, histology, and biomarkers for HF between groups.

Results: A total of 30 mice survived during the study period and were analyzed: CON (n=9), DOX (n=9) and ET-DOX (n=12). There was no significant difference in left ventricular ejection fraction (LVEF) or fractional shortening (FS) between DOX and ET-DOX groups. The ET-DOX group had a significantly lower soluble ST2 level (176.6±44.1 vs. 225.4±60.5 pg/mL, p=0.021) compared to the DOX group. Also similar between the ET-DOX and the DOX groups were the serum N-terminal prohormone of brain natriuretic peptide (30.3±12.5 vs. 34.0±21.7 pg/mL, p=0.849), troponin I (685.7±99.2 vs. 722.5±126.7 pg/mL, p=0.766), and neutrophil gelatinase-associated lipocalin (324.3±82.4 vs. 312.7±68.2 pg/mL, p=0.922) levels. Histologically, there was no significant difference in degree of perivascular fibrosis between DOX and ET-DOX groups.

Conclusions: Endurance ET is effective for preventing increases in serum soluble ST2 in mice treated with DOX.