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Alterations in Left Ventricular Preload Dynamically Regulate Cardiac Fibroblast Signaling
Author(s) -
Galantowicz Maarten L,
Guggilam Anuradha,
Cismowski Mary J,
Zhang Xiaojin,
West Thomas A,
Lucchesi Pamela A
Publication year - 2012
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.26.1_supplement.1060.17
Subject(s) - ctgf , extracellular matrix , smad , preload , medicine , fibrosis , transforming growth factor , endocrinology , hemodynamics , connective tissue , heart failure , signal transduction , chemistry , growth factor , microbiology and biotechnology , biology , pathology , receptor
Left ventricular (LV) hemodynamic volume overload (VO) inhibits cardiac fibrosis in vivo . However, the effects of hemodynamic load changes on connective tissue growth factor (CTGF) and TGF‐β1induced extracellular matrix (ECM) proteins are poorly understood. This study investigated the impact of load‐driven changes on cardiac fibroblast (CF) phenotype and signaling. Methods Sprague‐Dawley rats underwent sham/aortocaval fistula (ACF) surgery to induce VO heart failure for 4 weeks (compensatory stage), followed by a load reversal procedure in a subset of rats. Primary cultured LV CFs were obtained at 5 day post VO reversal, and ECM signaling molecules were studied by protein and gene expression profiling. Results Collagen 1 secretion was decreased in both ACF and reversal CFs, while CTGF mRNA expression decreased only in ACF CFs, consistent with an anti‐fibrotic phenotype. Interestingly, ACF and reversal CFs demonstrated increased TGF‐β1 mRNA expression and similar Smad activation in response to exogenous TGF‐ β1. However, β1‐integrin expression and downstream AKT signaling was suppressed in ACF CFs compared to sham, but normalized following VO reversal. Conclusion These data suggest that hemodynamic load modulates CF signaling and secretion of ECM proteins. Molecular profiling is necessary to understand how LV hemodynamic changes impact CF‐dependent ECM regulation.