Document Detail

TGF-beta1 overexpression: a mechanism of diastolic filling dysfunction in the aged population.
MedLine Citation:
PMID:  15095844     Owner:  NLM     Status:  MEDLINE    
The prevalence of cardiovascular disease in the United States dramatically increases with age. A hallmark feature of the aged myocardium is increased fibrosis resulting in diastolic dysfunction. Moreover, the survival of patients subsequent to a myocardial infarction is inversely related to age because of a certain extent to maladaptive remodeling mediated by cardiac fibroblasts. Our hypothesis is that cardiac fibroblast (CF) dysfunction results in overexpressed TGF-beta1 leading to increased cardiac collagen content in the aged population. TGF-beta1 stimulates the synthesis of the extracellular matrix proteins, including collagen in the cardiac tissues. The RT-PCR analysis of mRNA expression of TGF-beta1 of the CF was increased by 43% in the aged mice as compared to the younger. The stiffness of the left ventricle is expressed with the slope of the end-diastolic pressure-volume relationship parameter, beta (mmHg/microL). In a mouse model, we demonstrated that beta was 0.30 +/- 0.05 in the young as compared to 0.52 +/- 0.10 in the aged (p < .05). The ventricular stiffness was associated with the myocardial collagen content; namely, young versus the aged was 9.5 +/- 4.0 as compared to 16.4 +/- 2.3% of total protein, respectively (p < .05). In conclusion, the gene structure-function relationships support our hypothesis that cardiac fibroblast disregulation contributes to diastolic filling dysfunction in elderly persons. These data provide a potential contributory mechanism for diastolic dysfunction that may be vital in caring for the aged open-heart surgical patient.
Douglas F Larson; Rene Ingham; Cory M Alwardt; Bo Yang
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of extra-corporeal technology     Volume:  36     ISSN:  0022-1058     ISO Abbreviation:  J Extra Corpor Technol     Publication Date:  2004 Mar 
Date Detail:
Created Date:  2004-04-20     Completed Date:  2004-07-06     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0267637     Medline TA:  J Extra Corpor Technol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  69-74     Citation Subset:  T    
Circulatory Science Graduate Perfusion Program, Sarver Heart Center, The University of Arizona College of Medicine, Tucson, Arizona, USA.
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MeSH Terms
Age Factors
Collagen / pharmacology
Diastole / physiology*
Extracellular Matrix / pathology
Fibrosis / physiopathology*
Interleukin-10 / genetics
Mice, Inbred C57BL
RNA, Messenger / analysis
Random Allocation
Transforming Growth Factor beta / metabolism*
Ventricular Dysfunction, Left / metabolism*,  physiopathology
Reg. No./Substance:
0/RNA, Messenger; 0/Transforming Growth Factor beta; 130068-27-8/Interleukin-10; 9007-34-5/Collagen

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