PMID- 22556331
OWN - NLM
STAT- MEDLINE
DCOM- 20121009
LR  - 20220331
IS  - 1524-4636 (Electronic)
IS  - 1079-5642 (Linking)
VI  - 32
IP  - 8
DP  - 2012 Aug
TI  - Brain-derived neurotrophic factor protects against cardiac dysfunction after 
      myocardial infarction via a central nervous system-mediated pathway.
PG  - 1902-9
LID - 10.1161/ATVBAHA.112.248930 [doi]
AB  - OBJECTIVE: The central nervous system is thought to influence the regulation of 
      the cardiovascular system in response to humoral and neural signals from 
      peripheral tissues, but our understanding of the molecular mechanisms involved is 
      still quite limited. METHODS AND RESULTS: Here, we demonstrate a central nervous 
      system-mediated mechanism by which brain-derived neurotrophic factor (BDNF) has a 
      protective effect against cardiac remodeling after myocardial infarction (MI). We 
      generated conditional BDNF knockout mice, in which expression of BDNF was 
      systemically reduced, by using the inducible Cre-loxP system. Two weeks after MI 
      was induced surgically in these mice, systolic function was significantly 
      impaired and cardiac size was markedly increased in conditional BDNF knockout 
      mice compared with controls. Cardiomyocyte death was increased in these mice, 
      along with decreased expression of survival molecules. Deletion of the BDNF 
      receptor (tropomyosin-related kinase B) from the heart also led to the 
      exacerbation of cardiac dysfunction after MI. The plasma levels of BDNF were 
      markedly increased after MI, and this increase was associated with the 
      upregulation of BDNF expression in the brain, but not in the heart. Ablation of 
      afferent nerves from the heart or genetic disruption of neuronal BDNF expression 
      inhibited the increase of plasma BDNF after MI and led to the exacerbation of 
      cardiac dysfunction. Peripheral administration of BDNF significantly restored the 
      cardiac phenotype of neuronal BDNF-deficient mice. CONCLUSIONS: These results 
      suggest that BDNF expression is upregulated by neural signals from the heart 
      after MI and then protects the myocardium against ischemic injury.
FAU - Okada, Sho
AU  - Okada S
AD  - Department of Cardiovascular Science and Medicine, Chiba University Graduate 
      School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
FAU - Yokoyama, Masataka
AU  - Yokoyama M
FAU - Toko, Haruhiro
AU  - Toko H
FAU - Tateno, Kaoru
AU  - Tateno K
FAU - Moriya, Junji
AU  - Moriya J
FAU - Shimizu, Ippei
AU  - Shimizu I
FAU - Nojima, Aika
AU  - Nojima A
FAU - Ito, Takashi
AU  - Ito T
FAU - Yoshida, Yohko
AU  - Yoshida Y
FAU - Kobayashi, Yoshio
AU  - Kobayashi Y
FAU - Katagiri, Hideki
AU  - Katagiri H
FAU - Minamino, Tohru
AU  - Minamino T
FAU - Komuro, Issei
AU  - Komuro I
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120503
PL  - United States
TA  - Arterioscler Thromb Vasc Biol
JT  - Arteriosclerosis, thrombosis, and vascular biology
JID - 9505803
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
CIN - Arterioscler Thromb Vasc Biol. 2012 Aug;32(8):1749-50. PMID: 22815337
MH  - Animals
MH  - Brain/*physiology
MH  - Brain-Derived Neurotrophic Factor/blood/*physiology
MH  - Mice
MH  - Mice, Knockout
MH  - Myocardial Infarction/*physiopathology
MH  - Receptor, trkB/physiology
MH  - Signal Transduction
MH  - Systole
MH  - Ventricular Remodeling
EDAT- 2012/05/05 06:00
MHDA- 2012/10/10 06:00
CRDT- 2012/05/05 06:00
PHST- 2012/05/05 06:00 [entrez]
PHST- 2012/05/05 06:00 [pubmed]
PHST- 2012/10/10 06:00 [medline]
AID - ATVBAHA.112.248930 [pii]
AID - 10.1161/ATVBAHA.112.248930 [doi]
PST - ppublish
SO  - Arterioscler Thromb Vasc Biol. 2012 Aug;32(8):1902-9. doi: 
      10.1161/ATVBAHA.112.248930. Epub 2012 May 3.