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Transcriptional Regulation of Cardiomyocyte PPAR‐Alpha by Stretch
Author(s) -
Rodriguez Jessica,
Case Natasha,
Li Luge,
Rubin Janet,
Willis Monte S
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.928.4
Subject(s) - peroxisome proliferator activated receptor , peroxisome , transcription factor , messenger rna , receptor , endocrinology , medicine , myocyte , alpha (finance) , microbiology and biotechnology , heart failure , biology , chemistry , gene , biochemistry , construct validity , nursing , patient satisfaction
The heart is a highly metabolically active organ that derives its energy from mainly the oxidation of fatty acids (70‐80%) and to a lesser extent glucose (20‐30%). During the development of heart failure, cardiomyocytes metabolically adapt by switching its energy substrate preference to glucose. While members of the PPAR (peroxisome proliferator‐activated receptor) transcription factor family are required for this metabolic switch, the external factors that regulate PPAR activity have not been identified. In the present study, we identify that biomechanical stretch of cardiomyocytes leads to the transcriptional regulation of PPAR family members. The HL‐1 cardiomyocyte cell line was subjected to a 24 hour time course of cyclical (20 cycles/minute) unidirectional stretch (15%) using the Flexcell® Tension Plus(tm) System. By Real Time PCR analysis, we identified characteristic responses of the early response genes to stretch, with significant increases in cFos and BNP mRNA peaking at 15‐30 mins. In response to stretch, mRNA levels of PPAR‐α and PPAR‐ β/d decreased in a time dependent manner, however, only PPAR‐α protein levels were modulated. These studies identify for the first time a model to investigate how biomechanical stretch is transduced into changes in cardiomyocyte metabolism, a key process in the development of heart failure.