Document Detail


A murine model of isolated cardiac steatosis leads to cardiomyopathy.
MedLine Citation:
PMID:  21220706     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Lipid accumulation in the heart is associated with obesity and diabetes mellitus and may play an important role in the pathogenesis of heart failure seen in this patient population. Stored triglycerides are synthesized by the enzyme diacylglycerol acyl transferase (DGAT). We hypothesized that forced expression of DGAT1 in the cardiac myocyte would result in increased lipid accumulation and heart dysfunction. A cardiac myocyte-selective DGAT1 transgenic mouse was created and demonstrated increased lipid accumulation in the absence of hyperglycemia, plasma dyslipidemia or differences in body weight. Over time, expression of DGAT1 in the heart resulted in the development of a significant cardiomyopathy. Echocardiography revealed diastolic dysfunction with increased early mitral inflow velocity to late mitral inflow velocity ratio and decreased deceleration time, suggesting a restrictive pattern in the transgenic mice. Moderate systolic dysfunction was also seen at 52 weeks. Histological analysis showed increased cardiac fibrosis and increased expression of procollagen type 1A, matrix metalloproteinase 2, and tissue inhibitor of matrix metalloproteinase 2 in the transgenic mice. Mitochondrial biogenesis was reduced in the transgenic hearts, as was expression of cytochrome c oxidase 1 and cytochrome c. Expression of key transcription factors important in the regulation of mitochondrial biogenesis were reduced. These findings suggest that triglyceride accumulation, in the absence of systemic metabolic derangement, results in cardiac dysfunction and decreased mitochondrial biogenesis.
Authors:
Denis J Glenn; Feng Wang; Minobu Nishimoto; Michelle C Cruz; Yoshikazu Uchida; Walter M Holleran; Yan Zhang; Yerem Yeghiazarians; David G Gardner
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-01-10
Journal Detail:
Title:  Hypertension     Volume:  57     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-01-20     Completed Date:  2011-04-22     Revised Date:  2014-09-05    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  216-22     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Animals, Newborn
Blotting, Western
Cardiomyopathies / metabolism*,  pathology,  physiopathology
Cells, Cultured
Cytochromes c / metabolism
Diacylglycerol O-Acyltransferase / genetics,  metabolism*
Disease Models, Animal
Fatty Acids / metabolism*
Female
Fibrosis
Gene Expression
Lipid Metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Inbred DBA
Mice, Transgenic
Mitochondria / metabolism
Myocardium / metabolism*,  pathology
Myocytes, Cardiac / metabolism,  pathology
Rats
Reverse Transcriptase Polymerase Chain Reaction
Time Factors
Triglycerides / metabolism
Grant Support
ID/Acronym/Agency:
F32 HL074643/HL/NHLBI NIH HHS; HL 086158/HL/NHLBI NIH HHS; HL 45637/HL/NHLBI NIH HHS; K08 HL095735/HL/NHLBI NIH HHS; K08 HL095735-02/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Fatty Acids; 0/Triglycerides; 9007-43-6/Cytochromes c; EC 2.3.1.20/Dgat1 protein, mouse; EC 2.3.1.20/Diacylglycerol O-Acyltransferase
Comments/Corrections
Comment In:
Hypertension. 2011 Feb;57(2):148-50   [PMID:  21220703 ]

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


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