Document Detail


Mammalian target of rapamycin is a critical regulator of cardiac hypertrophy in spontaneously hypertensive rats.
MedLine Citation:
PMID:  19884565     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Evidence exists that protein kinase C and the mammalian target of rapamycin are important regulators of cardiac hypertrophy. We examined the contribution of these signaling kinases to cardiac growth in spontaneously hypertensive rats (SHRs). Systolic blood pressure was increased (P<0.001) at 10 weeks in SHRs versus Wistar-Kyoto controls (162+/-3 versus 128+/-1 mm Hg) and was further elevated (P<0.001) at 17 weeks in SHRs (184+/-7 mm Hg). Heart:body weight ratio was not different between groups at 10 weeks but was 22% greater (P<0.01) in SHRs versus Wistar-Kyoto controls at 17 weeks. At 10 weeks, activation of Akt and S6 ribosomal protein was greater (P<0.01) in SHRs but returned to normal by 17 weeks. In contrast, SHRs had protein kinase C activation only at 17 weeks. To determine whether mammalian target of rapamycin regulates the initial development of hypertrophy, rats were treated with rapamycin (2 mg/kg per day IP) or saline vehicle from 13 to 16 weeks of age. Rapamycin inhibited cardiac mammalian target of rapamycin in SHRs, as evidenced by reductions (P<0.001) in phosphorylation of S6 ribosomal protein and eukaryotic translation initiation factor-4E binding protein 1. Rapamycin treatment also reduced (P<0.001) heart weight and hypertrophy by 47% and 53%, respectively, in SHRs in spite of increased (P<0.001) systolic blood pressure versus untreated SHRs (213+/-8 versus 189+/-6 mm Hg). Atrial natriuretic peptide, brain natriuretic peptide, and cardiac function were unchanged between SHRs treated with rapamycin or vehicle. These data show that mammalian target of rapamycin is required for the development of cardiac hypertrophy evoked by rising blood pressure in SHRs.
Authors:
Will Soesanto; Han-Yi Lin; Eric Hu; Shane Lefler; Sheldon E Litwin; Sandra Sena; E Dale Abel; J David Symons; Thunder Jalili
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-11-02
Journal Detail:
Title:  Hypertension     Volume:  54     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2009 Dec 
Date Detail:
Created Date:  2009-11-20     Completed Date:  2009-12-17     Revised Date:  2013-05-31    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1321-7     Citation Subset:  IM    
Affiliation:
College of Health, University of Utah, Salt Lake City, UT 84112, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibiotics, Antineoplastic / pharmacology
Blood Pressure / physiology
Cardiomegaly / etiology*,  metabolism*,  pathology
Carrier Proteins / metabolism*
Hypertension, Renal / complications*,  metabolism*
Male
Phosphotransferases (Alcohol Group Acceptor) / metabolism*
Protein Kinase C / metabolism
Proto-Oncogene Proteins c-akt / metabolism
Rats
Rats, Inbred SHR
Rats, Inbred WKY
Ribosomal Protein S6 / metabolism
Signal Transduction / physiology
Sirolimus / pharmacology
TOR Serine-Threonine Kinases
Grant Support
ID/Acronym/Agency:
1R15HL085226/HL/NHLBI NIH HHS; 1R15HL091493-01/HL/NHLBI NIH HHS; R15 HL085226-01/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Antibiotics, Antineoplastic; 0/Carrier Proteins; 0/Ribosomal Protein S6; 53123-88-9/Sirolimus; EC 2.7.1.-/Phosphotransferases (Alcohol Group Acceptor); EC 2.7.1.1/TOR Serine-Threonine Kinases; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 2.7.11.13/Protein Kinase C
Comments/Corrections
Comment In:
Hypertension. 2009 Dec;54(6):1221-2   [PMID:  19884561 ]

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