Abstract 340: Myocyte-borne Bdnf is Essential to Limit Post-ischemic Cardiac Injury and Dysfunction
Jun, S; Agrimi, J; Cannavo, A; Keceli, G; Oeing, CU; Eremiev, A; Marcucci, L; Megighian, A; RENGO, G; Koch, WJ; Paolocci, N
Published in: Circulation Research
(BDNF)/
(TrkB) signaling is essential for normal cardiac contraction/relaxation. Alterations in this pathway, i.e., defective neuronal BDNF, account for post-ischemic cardiac injury. Less clear, however, is whether myocyte-borne BDNF has a role in this setting. We generated myocyte-selective BDNF knock-out (myoBDNF
) mice, using Myh6-Cre mice crossed with BDNF
mice, confirming
deletion via RT-PCR in isolated myocytes. Hearts from 12-wk old myoBDNF
mice and WT littermates underwent global ischemia (30 min) and reperfusion (2 h). At this age, the two strains had similar left ventricular (LV) sizes and fractional shortening [63±1.1 (WT)
60±1.2% (myoBDNF
)]. At reperfusion, myoBDNF
hearts displayed larger infarct size compared to WT (38±3
14±2%, n=9, p<.0001) and worsened LV functional recovery (
). For example, the rate-pressure product recuperated only by 14±1.5 in myoBDNF
mice
36±3% in WT (p<.0001). The two groups had similar heart rates at 2 h reperfusion, however myoBDNF
mice markedly lost their contractility [dP/dt
= 436±58
1407±142 mmHg/sec (WT), p< .0001], likely due to the exacerbated myocyte loss. Accordingly, post-ischemic troponin I release was significantly higher in myoBDNF
than in WT mice (0.9±0.04
1.3±0.04 ng/ml, p<.0002). Thus, deleting
in myocytes severely limits recovery after ischemia, directly linking myocyte-borne BDNF to the heart response to injury. Therefore, preserving or enhancing autologous myocyte BDNF generation offers new avenues to counter cardiac ischemic injury and subsequent heart failure progression.
