Relaxation of the Human Type 2 Diabetic Myocardium
Lingam, Shivanjali
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Cite this item:
Lingam, S. (2013). Relaxation of the Human Type 2 Diabetic Myocardium (Thesis, Master of Science). University of Otago. Retrieved from http://hdl.handle.net/10523/4149
Permanent link to OUR Archive version:
http://hdl.handle.net/10523/4149
Abstract:
Type 2 diabetes mellitus (T2DM) is associated with a wide spectrum of cardiovascular abnormalities, which are proposed to range from heart failure with preserved ejection fraction (HFpEF (diastolic dysfunction)) to heart failure with reduced ejection fraction (systolic dysfunction). Accumulating evidence from diabetic rodent models indicates that impaired relaxation underlies T2DM-induced HFpEF; however, the aetiology of impaired relaxation in human T2DM remains undefined.
Hence, this study aimed to investigate the expression of sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA2a) and its negative regulator, phospholamban (PLB), both involved in cardiac relaxation, and their contribution to the reduced relaxation phenotype in T2DM patients with no systolic dysfunction (EF > 40%).
Using Picro-Sirius red staining, the current study revealed that fibrosis was significantly higher in right atrial appendages of T2DM patients (n = 7) compared to non-DM patients (n = 7, p < 0.05). Paradoxically, subsequent western blotting experiments revealed similar SERCA2a expression and reduced PLB (p < 0.05) expression in RAAs of non-DM patients (n = 18) compared to T2DM patients (n = 10) leading to an increased SERCA2a:PLB expression ratio in the T2DM group.
The increased SERCA2a:PLB expression ratio in the human T2DM myocardium compared to non-DM myocardium suggests an augmentation in SERCA2a activity, indicative of improved relaxation, which could reflect a compensatory mechansim to attempt to maintain cardiac diastolic function in T2DM before the onset of systolic dysfunction.
Date:
2013
Advisor:
Jones, Peter; Lamberts, Regis
Degree Name:
Master of Science
Degree Discipline:
Physiology
Publisher:
University of Otago
Keywords:
Human; type2diabetes; SERCA2a; PLB
Research Type:
Thesis
Languages:
English
Collections
- Thesis - Masters [4213]
- Physiology [174]