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Left ventricle structural remodeling in the prediabetic goto‐kakizaki rat
Author(s) -
Singh Jaipaul,
D'souza Alicia
Publication year - 2011
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.25.1_supplement.1031.2
Subject(s) - medicine , endocrinology , extracellular matrix , ctgf , muscle hypertrophy , fibronectin , transforming growth factor beta , transforming growth factor , ventricular remodeling , ventricle , fibrosis , growth factor , biology , microbiology and biotechnology , heart failure , receptor
This study tested the hypothesis that experimental prediabetes can elicit structural remodelling in the left ventricle (LV). Prediabetic Goto Kakizaki (GK) rats and age‐matched Wistar controls were used to assess LV and plasma Transforming Growth Factor β1 (TGFβ1) activity, myocyte hypertrophy, extracellular matrix (ECM) deposition, activation of the pro‐hypertrophic Akt‐p70S6k pathway and gene expression profile of the ECM. LV remodelling in the GK rat presented with larger hearts, marked hypertrophy of cardiomyocytes and increased ECM deposition. Molecular derangements underlying this phenotype included expression of B‐type natriuretic peptide and α‐Skeletal actin, activation of the Akt‐p70S6k pathway and altered gene expression profile of key components (Collagen 1α, fibronectin) and modulators (matrix metalloproteinases 2 and 9, Connective tissue growth factor) of the ECM. These changes were correlated with parallel findings of increased TGFβ1 transcription and activation in the LV and elevated active TGFβ1 in plasma of GK rats compared to controls. Current data suggest that ventricular decompensation occurring in advanced diabetic cardiomyopathy may have origins in pro‐fibrotic and pro‐hypertrophic mechanisms triggered before the onset of T2DM. TGFβ1 activity may represent a key intermediary in this process.