Document Detail


Peroxisome proliferator--activated receptor alpha gene regulates left ventricular growth in response to exercise and hypertension.
MedLine Citation:
PMID:  11864924     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Left ventricular hypertrophy (LVH) occurs as an adaptive response to a physiological (such as exercise) or pathological (valvular disease, hypertension, or obesity) increase in cardiac work. The molecular mechanisms regulating the LVH response are poorly understood. However, inherited defects in fatty acid oxidation are known to cause severe early-onset cardiac hypertrophy. Peroxisome proliferator--activated receptor alpha (PPARalpha) regulates genes responsible for myocardial fatty acid oxidation and is downregulated during cardiac hypertrophy, concomitant with the switch from fatty acid to glucose utilization. METHODS AND RESULTS: The role of PPARalpha in left ventricular growth was investigated in 144 young male British Army recruits undergoing a 10-week physical training program and in 1148 men and women participating in the echocardiographic substudy of the Third Monitoring Trends and Determinants in Cardiovascular Disease (MONICA) Augsburg study. A G/C polymorphism in intron 7 of the PPARalpha gene significantly influenced left ventricular (LV) growth in response to exercise (P=0.009). LV mass increased by 6.7 +/- 1.5 g in G allele homozygotes but was significantly greater in heterozygotes for the C allele (11.8 +/- 1.9 g) and in CC homozygotes (19.4 +/- 4.2 g). Likewise, C allele homozygotes had significantly higher LV mass, which was greater still in hypertensive subjects, and a higher prevalence of LVH in the Third MONICA Augsburg study. CONCLUSIONS: We demonstrate that variation in the PPARalpha gene influences human left ventricular growth in response to exercise and hypertension, indicating that maladaptive cardiac substrate utilization can play a causative role in the pathogenesis of LVH.
Authors:
Yalda Jamshidi; Hugh E Montgomery; Hans-Werner Hense; Saul G Myerson; Ines Pineda Torra; Bart Staels; Michael J World; Angela Doering; Jeanette Erdmann; Christian Hengstenberg; Steve E Humphries; Heribert Schunkert; David M Flavell
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Publication Detail:
Type:  Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Circulation     Volume:  105     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2002 Feb 
Date Detail:
Created Date:  2002-02-26     Completed Date:  2002-03-04     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  950-5     Citation Subset:  AIM; IM    
Affiliation:
Centre for Cardiovascular Genetics, Department of Medicine, University College London Medical School, London, UK.
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MeSH Terms
Descriptor/Qualifier:
Adaptation, Physiological
Adult
Aged
DNA Mutational Analysis
Disease Progression
Echocardiography
Electrocardiography
Exercise*
Female
Gene Frequency
Genetic Testing
Heart Ventricles / physiopathology*
Heterozygote
Homozygote
Humans
Hypertension / complications,  physiopathology*
Hypertrophy, Left Ventricular / etiology,  physiopathology*
Male
Middle Aged
Polymorphism, Genetic
Receptors, Cytoplasmic and Nuclear / genetics*
Risk Assessment
Transcription Factors / genetics*
Chemical
Reg. No./Substance:
0/Receptors, Cytoplasmic and Nuclear; 0/Transcription Factors
Comments/Corrections
Comment In:
Circulation. 2002 Mar 5;105(9):1025-7   [PMID:  11877347 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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