PMID- 30311496
OWN - NLM
STAT- MEDLINE
DCOM- 20190909
LR  - 20211204
IS  - 1522-1539 (Electronic)
IS  - 0363-6135 (Linking)
VI  - 315
IP  - 6
DP  - 2018 Dec 1
TI  - Effects of exercise training and TrkB blockade on cardiac function and BDNF-TrkB 
      signaling postmyocardial infarction in rats.
PG  - H1821-H1834
LID - 10.1152/ajpheart.00245.2018 [doi]
AB  - Exercise training is beneficial for preserving cardiac function postmyocardial 
      infarction (post-MI), but the underlying mechanisms are not well understood. We 
      investigated one possible mechanism, brain-derived neurotrophic factor 
      (BDNF)-tropomyosin-related kinase B (TrkB) signaling, with the TrkB blocker 
      ANA-12 (0.5 mg.kg(-1).day(-1)). Male Wistar rats underwent sham surgery or 
      ligation of the left descending coronary artery. The surviving MI rats were 
      allocated as follows: sedentary MI rats treated with vehicle, exercise-trained MI 
      rats treated with vehicle, and exercise-trained MI rats treated with ANA-12. 
      Exercise training was done 5 days/wk for 4 wk on a motor-driven treadmill. At the 
      end, left ventricular (LV) function was evaluated by echocardiography and a 
      Millar catheter. Mature BDNF and downstream effectors of BDNF-TrkB signaling, 
      Ca(2+)/calmodulin-dependent protein kinase II (CaMKII), Akt, and AMP-activated 
      protein kinase (AMPK), were assessed in the noninfarct area of the LV by Western 
      blot analysis. Exercise training increased stroke volume and cardiac index and 
      attenuated the decrease in ejection fraction (EF) and increase in LV 
      end-diastolic pressure post-MI. ANA-12 blocked the improvement of EF and 
      attenuated the increases in stroke volume and cardiac index but did not affect LV 
      end-diastolic pressure. Exercise training post-MI prevented decreases in mature 
      BDNF, phosphorylated (p-)CaMKII, p-Akt, and p-AMPKalpha expression. These effects 
      were all blocked by ANA-12 except for p-AMPKalpha. In conclusion, the 
      exercise-induced improvement of EF is mediated by the BDNF-TrkB axis and the 
      downstream effectors CaMKII and Akt. BDNF-TrkB signaling appears to contribute to 
      the improvement in systolic function by exercise training. NEW & NOTEWORTHY 
      Exercise training improves ejection fraction and left ventricular end-diastolic 
      pressure (LVEDP) and increases stroke volume and cardiac index in rats 
      postmyocardial infarction (post-MI). The improvement of EF but not LVEDP is 
      mediated by activation of the brain-derived neurotrophic factor 
      (BDNF)-tropomyosin-related kinase B (TrkB) axis and downstream effectors 
      Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and Akt. This suggests 
      that activation of BDNF-TrkB signaling and CaMKII and Akt is a promising target 
      to attenuate progressive cardiac dysfunction post-MI.
FAU - Lee, Heow Won
AU  - Lee HW
AD  - Brain and Heart Research Group, University of Ottawa Heart Institute , Ottawa, ON 
      , Canada.
FAU - Ahmad, Monir
AU  - Ahmad M
AD  - Brain and Heart Research Group, University of Ottawa Heart Institute , Ottawa, ON 
      , Canada.
FAU - Weldrick, Jonathan J
AU  - Weldrick JJ
AD  - Department of Cellular and Molecular Medicine, Faculty of Medicine, University of 
      Ottawa , Ottawa, ON , Canada.
FAU - Wang, Hong-Wei
AU  - Wang HW
AD  - Brain and Heart Research Group, University of Ottawa Heart Institute , Ottawa, ON 
      , Canada.
FAU - Burgon, Patrick G
AU  - Burgon PG
AD  - Department of Cellular and Molecular Medicine, Faculty of Medicine, University of 
      Ottawa , Ottawa, ON , Canada.
FAU - Leenen, Frans H H
AU  - Leenen FHH
AD  - Brain and Heart Research Group, University of Ottawa Heart Institute , Ottawa, ON 
      , Canada.
LA  - eng
GR  - MOP-136923/CIHR/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20181012
PL  - United States
TA  - Am J Physiol Heart Circ Physiol
JT  - American journal of physiology. Heart and circulatory physiology
JID - 100901228
RN  - 0 (ANA 12 compound)
RN  - 0 (Azepines)
RN  - 0 (Benzamides)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Protein Kinase Inhibitors)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.10.1 (Ntrk2 protein, rat)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 2)
RN  - EC 2.7.11.3 (AMP-Activated Protein Kinase Kinases)
SB  - IM
MH  - AMP-Activated Protein Kinase Kinases
MH  - Animals
MH  - Azepines/therapeutic use
MH  - Benzamides/therapeutic use
MH  - Blood Pressure
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism
MH  - Heart Ventricles/*metabolism/physiopathology
MH  - Male
MH  - Myocardial Infarction/drug therapy/*therapy
MH  - Physical Conditioning, Animal/*methods
MH  - Protein Kinase Inhibitors/therapeutic use
MH  - Protein Kinases/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Receptor, trkB/*antagonists & inhibitors/metabolism
MH  - Signal Transduction
MH  - Stroke Volume
OTO - NOTNLM
OT  - ANA-12
OT  - brain-derived neurotrophic factor-tropomyosin-related kinase B signaling
OT  - exercise training
OT  - heart failure
OT  - tropomyosin-related kinase B blockade
EDAT- 2018/10/13 06:00
MHDA- 2019/09/10 06:00
CRDT- 2018/10/13 06:00
PHST- 2018/10/13 06:00 [pubmed]
PHST- 2019/09/10 06:00 [medline]
PHST- 2018/10/13 06:00 [entrez]
AID - 10.1152/ajpheart.00245.2018 [doi]
PST - ppublish
SO  - Am J Physiol Heart Circ Physiol. 2018 Dec 1;315(6):H1821-H1834. doi: 
      10.1152/ajpheart.00245.2018. Epub 2018 Oct 12.