PMID- 17395699
OWN - NLM
STAT- MEDLINE
DCOM- 20071002
LR  - 20211203
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 148
IP  - 7
DP  - 2007 Jul
TI  - Rapamycin prevents thyroid hormone-induced cardiac hypertrophy.
PG  - 3477-84
AB  - Thyroid hormones (THs) have many effects on the cardiovascular system including 
      cardiac hypertrophy. Although THs induce cardiac hypertrophy, the mechanism 
      through which they exert this effect is unknown. We previously found that THs 
      activate signaling related to increased protein synthesis [mammalian target of 
      rapamycin (mTOR) and p70 S6 kinase] in the heart. It is unknown whether this 
      activation contributes to TH-induced hypertrophy or whether it is merely 
      incidental. In this study, we used rapamycin to inhibit mTOR function in mice and 
      neonatal cardiomyocyte cultures treated with THs to test whether mTOR/S6 kinase 
      signaling is involved in TH-mediated cardiac hypertrophy. C57 mice were treated 
      with T4 for 3 d, 1 wk, 2 wk, or 1 month with either placebo, T4 (50 microg/100 g 
      body weight.d), rapamycin (200 microg/100 g body weight.d) or T4/rapamycin by sc 
      slow-release pellets. At the end of the treatment period, hemodynamics and 
      physical data were collected and hearts were frozen for Western blot analysis or 
      myocytes were isolated. The effects of T3 and rapamycin were also investigated 
      using neonatal cardiomyocytes. THs activated specific components of the AKT 
      signaling pathway in vivo and in vitro. THs induced cardiac hypertrophy, which 
      was completely inhibited by rapamycin. Our results suggest that TH-induced 
      hypertrophy is mediated by AKT/mTOR/S6 kinase signaling, which is important in 
      the regulation of protein synthesis, a hallmark of cardiac hypertrophy.
FAU - Kuzman, James A
AU  - Kuzman JA
AD  - stanford Research/University of South Dakota, Sanford School of Medicine, 
      Cardiovascular Research Institute, 1100 East 21st Street, Suite 700, Sioux Falls, 
      South Dakota 57105, USA.
FAU - O'Connell, Timothy D
AU  - O'Connell TD
FAU - Gerdes, A Martin
AU  - Gerdes AM
LA  - eng
GR  - HL 62459/HL/NHLBI NIH HHS/United States
GR  - P20 RR017662/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20070329
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Thyroid Hormones)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - Q51BO43MG4 (Thyroxine)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Blotting, Western
MH  - Body Weight/drug effects
MH  - Cardiomegaly/chemically induced/metabolism/*prevention & control
MH  - Cell Shape/drug effects
MH  - Cell Size/drug effects
MH  - Cells, Cultured
MH  - Female
MH  - Heart/drug effects/physiopathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Myocardium/metabolism/pathology
MH  - Myocytes, Cardiac/cytology/drug effects/metabolism
MH  - Organ Size/drug effects
MH  - Phosphorylation/drug effects
MH  - Protein Kinases/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Random Allocation
MH  - Signal Transduction/drug effects
MH  - Sirolimus/administration & dosage/*pharmacology
MH  - TOR Serine-Threonine Kinases
MH  - Thyroid Hormones/administration & dosage/*pharmacology
MH  - Thyroxine/pharmacology
MH  - Time Factors
EDAT- 2007/03/31 09:00
MHDA- 2007/10/03 09:00
CRDT- 2007/03/31 09:00
PHST- 2007/03/31 09:00 [pubmed]
PHST- 2007/10/03 09:00 [medline]
PHST- 2007/03/31 09:00 [entrez]
AID - en.2007-0099 [pii]
AID - 10.1210/en.2007-0099 [doi]
PST - ppublish
SO  - Endocrinology. 2007 Jul;148(7):3477-84. doi: 10.1210/en.2007-0099. Epub 2007 Mar 
      29.