PMID- 22561297
OWN - NLM
STAT- MEDLINE
DCOM- 20120904
LR  - 20240109
IS  - 1522-1539 (Electronic)
IS  - 0363-6135 (Print)
IS  - 0363-6135 (Linking)
VI  - 303
IP  - 1
DP  - 2012 Jul
TI  - Cardiac mTOR protects the heart against ischemia-reperfusion injury.
PG  - H75-85
LID - 10.1152/ajpheart.00241.2012 [doi]
AB  - Cardiac mammalian target of rapamycin (mTOR) is necessary and sufficient to 
      prevent cardiac dysfunction in pathological hypertrophy. However, the role of 
      cardiac mTOR in heart failure after ischemic injury remains undefined. To address 
      this question, we used transgenic (Tg) mice with cardiac-specific overexpression 
      of mTOR (mTOR-Tg mice) to study ischemia-reperfusion (I/R) injury in two animal 
      models: 1) in vivo I/R injury with transient coronary artery ligation and 2) ex 
      vivo I/R injury in Langendorff-perfused hearts with transient global ischemia. At 
      28 days after I/R, mortality was lower in mTOR-Tg mice than littermate control 
      mice [wild-type (WT) mice]. Echocardiography and MRI demonstrated that global 
      cardiac function in mTOR-Tg mice was preserved, whereas WT mice exhibited 
      significant cardiac dysfunction. Masson's trichrome staining showed that 28 days 
      after I/R, the area of interstitial fibrosis was smaller in mTOR-Tg mice compared 
      with WT mice, suggesting that adverse left ventricular remodeling is inhibited in 
      mTOR-Tg mice. In the ex vivo I/R model, mTOR-Tg hearts demonstrated improved 
      functional recovery compared with WT hearts. Perfusion with Evans blue after ex 
      vivo I/R yielded less staining in mTOR-Tg hearts than WT hearts, indicating that 
      mTOR overexpression inhibited necrosis during I/R injury. Expression of 
      proinflammatory cytokines, including IL-6 and TNF-alpha, in mTOR-Tg hearts was lower 
      than in WT hearts. Consistent with this, IL-6 in the effluent post-I/R injury was 
      lower in mTOR-Tg hearts than in WT hearts. These findings suggest that cardiac 
      mTOR overexpression in the heart is sufficient to provide substantial 
      cardioprotection against I/R injury and suppress the inflammatory response.
FAU - Aoyagi, Toshinori
AU  - Aoyagi T
AD  - Center for Cardiovascular Research, John A. Burns School of Medicine, University 
      of Hawaii, Honolulu, 96813, USA.
FAU - Kusakari, Yoichiro
AU  - Kusakari Y
FAU - Xiao, Chun-Yang
AU  - Xiao CY
FAU - Inouye, Brendan T
AU  - Inouye BT
FAU - Takahashi, Masaya
AU  - Takahashi M
FAU - Scherrer-Crosbie, Marielle
AU  - Scherrer-Crosbie M
FAU - Rosenzweig, Anthony
AU  - Rosenzweig A
FAU - Hara, Kenta
AU  - Hara K
FAU - Matsui, Takashi
AU  - Matsui T
LA  - eng
GR  - P30 GM103341/GM/NIGMS NIH HHS/United States
GR  - R01 HL098423/HL/NHLBI NIH HHS/United States
GR  - HL-094677/HL/NHLBI NIH HHS/United States
GR  - HL-098423/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20120504
PL  - United States
TA  - Am J Physiol Heart Circ Physiol
JT  - American journal of physiology. Heart and circulatory physiology
JID - 100901228
RN  - 9007-49-2 (DNA)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Autophagy
MH  - Blotting, Western
MH  - Coronary Vessels/physiology
MH  - DNA/genetics/isolation & purification
MH  - Fibrosis
MH  - In Vitro Techniques
MH  - Inflammation/genetics/pathology
MH  - Ligation
MH  - Magnetic Resonance Imaging
MH  - Male
MH  - Mice
MH  - Mice, Transgenic
MH  - Myocardial Ischemia/physiopathology
MH  - Myocardial Reperfusion Injury/diagnostic imaging/pathology/*prevention & control
MH  - Myocardium/pathology
MH  - Myocytes, Cardiac/pathology
MH  - Necrosis
MH  - Perfusion
MH  - Real-Time Polymerase Chain Reaction
MH  - TOR Serine-Threonine Kinases/genetics/*physiology
MH  - Ultrasonography
PMC - PMC3404649
EDAT- 2012/05/09 06:00
MHDA- 2012/09/05 06:00
PMCR- 2013/07/01
CRDT- 2012/05/08 06:00
PHST- 2012/05/08 06:00 [entrez]
PHST- 2012/05/09 06:00 [pubmed]
PHST- 2012/09/05 06:00 [medline]
PHST- 2013/07/01 00:00 [pmc-release]
AID - ajpheart.00241.2012 [pii]
AID - H-00241-2012 [pii]
AID - 10.1152/ajpheart.00241.2012 [doi]
PST - ppublish
SO  - Am J Physiol Heart Circ Physiol. 2012 Jul;303(1):H75-85. doi: 
      10.1152/ajpheart.00241.2012. Epub 2012 May 4.