TGF-β1 Overexpression: A Mechanism of Diastolic Filling Dysfunction in the Aged Population

Douglas F. Larson, Rene Ingham, Cory M. Alwardt, Bo Yang

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

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-β1 leading to increased cardiac collagen content in the aged population. TGF-β1 stimulates the synthesis of the extracellular matrix proteins, including collagen in the cardiac tissues. The RT-PCR analysis of mRNA expression of TGF-β1 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, β (mmHg/μL). In a mouse model, we demonstrated that β 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.

Original languageEnglish (US)
Pages (from-to)69-74
Number of pages6
JournalJournal of Extra-Corporeal Technology
Volume36
Issue number1
StatePublished - Mar 1 2004

Keywords

  • Aging
  • Conductance catheter
  • Diastolic function
  • Fibroblast
  • TGF-β

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Health Professions (miscellaneous)
  • Cardiology and Cardiovascular Medicine

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