Left ventricle structural remodelling in the prediabetic Goto-Kakizaki rat
- PMID: 21622965
- DOI: 10.1113/expphysiol.2011.058271
Left ventricle structural remodelling in the prediabetic Goto-Kakizaki rat
Abstract
This study tested the hypothesis that experimental prediabetes can elicit structural remodelling in the left ventricle (LV). Left ventricles isolated from 8-week-old male Goto-Kakizaki (GK) rats and age-matched male Wistar control rats were used to assess remodelling changes and underlying transforming growth factor β1 (TGFβ1) activity, prohypertrophic Akt-p70S6K1 signalling and gene expression profile of the extracellular matrix (ECM) using histological, immunohistochemical, immunoblotting and quantitative gene expression analyses. Prediabetes in GK rats was confirmed by impaired glucose tolerance and modestly elevated fasting blood glucose. Left ventricle remodelling in the GK rat presented with marked hypertrophy of cardiomyocytes and increased ECM deposition that together translated into increased heart size in the absence of ultrastructural changes or fibre disarray. Molecular derangements underlying this phenotype included recapitulation of the fetal gene phenotype markers B-type natriuretic peptide and α-skeletal muscle actin, activation of the Akt-p70S6K1 pathway and altered gene expression profile of key components (collagen 1α and fibronectin) and modulators of the ECM (matrix metalloproteinases 2 and 9 and connective tissue growth factor). 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 with control animals (Student's t test, P < 0.05 versus age-matched Wistar control animals for all parameters). This is the first report to describe LV structural remodelling in experimental prediabetes. The results suggest that ventricular decompensation pathognomonic of advanced diabetic cardiomyopathy may have possible origins in profibrotic and prohypertrophic mechanisms triggered before the onset of type 2 diabetes mellitus.
Comment in
-
Ventricular remodelling in prediabetes: the heart of the matter!Exp Physiol. 2011 Sep;96(9):829-30. doi: 10.1113/expphysiol.2011.059774. Exp Physiol. 2011. PMID: 21865533 No abstract available.
Similar articles
-
Chronic effects of mild hyperglycaemia on left ventricle transcriptional profile and structural remodelling in the spontaneously type 2 diabetic Goto-Kakizaki rat.Heart Fail Rev. 2014 Jan;19(1):65-74. doi: 10.1007/s10741-013-9376-9. Heart Fail Rev. 2014. PMID: 23430124
-
Long-term effects of type 2 diabetes mellitus on heart rhythm in the Goto-Kakizaki rat.Exp Physiol. 2008 Mar;93(3):362-9. doi: 10.1113/expphysiol.2007.040055. Epub 2007 Dec 21. Exp Physiol. 2008. PMID: 18156165
-
Chronic effects of type 2 diabetes mellitus on cardiac muscle contraction in the Goto-Kakizaki rat.Exp Physiol. 2007 Nov;92(6):1029-36. doi: 10.1113/expphysiol.2007.038703. Epub 2007 Aug 3. Exp Physiol. 2007. PMID: 17675413
-
Impaired glucose tolerance and insulinopenia in the GK-rat causes peripheral neuropathy.Diabetes Metab Res Rev. 2002 Nov-Dec;18(6):473-83. doi: 10.1002/dmrr.326. Diabetes Metab Res Rev. 2002. PMID: 12469361
-
Remodelling of cardiac extracellular matrix during beta-adrenergic stimulation: upregulation of SPARC in the myocardium of adult rats.J Mol Cell Cardiol. 1998 Aug;30(8):1505-14. doi: 10.1006/jmcc.1998.0714. J Mol Cell Cardiol. 1998. PMID: 9737937
Cited by
-
Interplay Between TGF-β Signaling and MicroRNA in Diabetic Cardiomyopathy.Cardiovasc Drugs Ther. 2023 Dec 20. doi: 10.1007/s10557-023-07532-2. Online ahead of print. Cardiovasc Drugs Ther. 2023. PMID: 38117422 Review.
-
Modelling Diabetic Cardiomyopathy: Using Human Stem Cell-Derived Cardiomyocytes to Complement Animal Models.Metabolites. 2022 Sep 3;12(9):832. doi: 10.3390/metabo12090832. Metabolites. 2022. PMID: 36144236 Free PMC article. Review.
-
Role of cannabinoids and the endocannabinoid system in modulation of diabetic cardiomyopathy.World J Diabetes. 2022 May 15;13(5):387-407. doi: 10.4239/wjd.v13.i5.387. World J Diabetes. 2022. PMID: 35664549 Free PMC article. Review.
-
Guidelines on models of diabetic heart disease.Am J Physiol Heart Circ Physiol. 2022 Jul 1;323(1):H176-H200. doi: 10.1152/ajpheart.00058.2022. Epub 2022 Jun 3. Am J Physiol Heart Circ Physiol. 2022. PMID: 35657616 Free PMC article. Review.
-
Bone Morphogenetic Protein 7 Gene Delivery Improves Cardiac Structure and Function in a Murine Model of Diabetic Cardiomyopathy.Front Pharmacol. 2021 Oct 8;12:719290. doi: 10.3389/fphar.2021.719290. eCollection 2021. Front Pharmacol. 2021. PMID: 34690762 Free PMC article.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical