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Age-dependent development of left ventricular wall thickness in type 2 diabetic (db/db) mice is associated with elevated low-density lipoprotein and triglyceride serum levels

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Abstract

Diabetic cardiomyopathy (DCM) is a disease of heart muscle that remains one of the leading causes of death in diabetic individuals. Shifts in substrate preference resulting in aberrant serum lipid content and enlarged left ventricular wall thickness are well-established characteristics associated with the development of DCM. As underlying mechanisms driving the onset of the DCM remain relatively unclear, this study sought to characterize age-dependent development of left ventricular (LV) wall thickness in diabetic (db/db) mice. Such data were compared with low-density lipoprotein (LDL) and triglyceride serum levels to assess whether any correlation exists between the parameters here investigated. For methods, db/db mice together with nondiabetic controls (n = six per group) were monitored from the age of 6–16 weeks. Mice were terminated each week to measure body weights, heart weights, liver weights, tibia length, and fasting plasma glucose levels. Heart tissues were stained with haematoxylin and eosin to measure LV wall and interventricular septum thickness together with an assessment of myocardial remodeling. Serum was collected weekly and used to measure LDL and triglyceride levels. Results showed that db/db mice presented significantly increased body weights, liver/body weight, and fasting plasma glucose levels from the age of 6–16 weeks. They further displayed a marked enlargement of LV wall and interventricular septum thickness from the age of 11 weeks, while increased heart weight/tibia length was recorded only from week 16. From week 11, the LV wall and interventricular septum thickness results corresponded with cardiac remodeling and raised LDL and triglyceride serum levels. In summary, age-dependent development of LV wall thickness in db/db mice is partially associated with increased LDL and triglyceride levels, elucidating a potential pathophysiological mechanism.

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Acknowledgements

This research was funded in part by the National Research Foundation (NRF) Thuthuka Programme Grant 87836 and the South Africa Medical Research Council’s Biomedical Research and Innovation Platform. The grantholders acknowledge that opinions, findings, and conclusions or recommendations expressed in any publication generated by the NRF supported research are those of the authors, and that the NRF accepts no liability whatsoever in this regard. Funding from Stellenbosch University and Ernst Ethel Erikson trust is also acknowledged. We would like to thank Charna Chapman, Desmond Linden, and Joritha van Heerden for technical support with animal work.

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Authors and Affiliations

  1. Biomedical Research and Innovation Platform (BRIP), Medical Research Council (MRC), P.O. Box 19070, Tygerberg, 7505, South Africa

    Phiwayinkosi V. Dludla, Kwazi B. Gabuza, Christo J. F. Muller, Johan Louw & Rabia Johnson

  2. Division of Medical Physiology, Faculty of Health Sciences, Stellenbosch University, Tygerberg, South Africa

    Phiwayinkosi V. Dludla, Christo J. F. Muller & Rabia Johnson

  3. Cardio-Metabolic Research Group (CMRG), Department of Physiological Sciences, Stellenbosch University, Stellenbosch, South Africa

    M. Faadiel Essop

  4. Department of Biochemistry and Microbiology, University of Zululand, KwaDlangezwa, 3886, South Africa

    Christo J. F. Muller & Johan Louw

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  1. Phiwayinkosi V. Dludla
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  2. M. Faadiel Essop
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  3. Kwazi B. Gabuza
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Correspondence to Phiwayinkosi V. Dludla.

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Dludla, P.V., Essop, M.F., Gabuza, K.B. et al. Age-dependent development of left ventricular wall thickness in type 2 diabetic (db/db) mice is associated with elevated low-density lipoprotein and triglyceride serum levels. Heart Vessels 32, 1025–1031 (2017). https://doi.org/10.1007/s00380-017-0978-3

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  • DOI: https://doi.org/10.1007/s00380-017-0978-3

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