Mitochondria are highly dynamic organelles which constantly undergo fusion and fission, processes essential to maintaining cardiac health. Recent experimental studies have highlighted altered morphology, with the appearance of both giant and small fragmented mitochondria observed in different models of heart failure. Our previous work on uraemic cardiomyopathy (UCM) has identified mitochondrial abnormalities and an increased susceptibility to injury. Our hypothesis is that altered morphology in UCM mitochondria may underpin this vulnerability.
Experimental uraemia was induced in male Sprague-Dawley rats via a subtotal nephrectomy. Cardiac hypertrophy was quantified using the heart weight-to-tibia length ratio (HW:TL) and the degree of uraemia and anaemia assessed using serum biochemistry. Mitochondrial dynamics in the heart were probed by investigating expression of mitofusin 2 (MFN2) and dynamin-related protein 1 (DRP1) using Western blotting. Alterations in cardiac mitochondrial size were evaluated in isolated mitochondria using flow cytometry and dynamic light scattering (DLS).
The heart weight-to-tibia length ratio was increased in uraemic animals reflecting a substantial hypertrophic response (HW:TL=0.39±0.01 uraemic vs 0.36±0.01 control). In addition, animals exhibited uraemia (serum creatinine=81.9±3 µM uraemic vs 34.8±1.5 µM control; serum urea=24.9±1.6 mM uraemic vs 13.1±0.6 mM control) and anaemia (packed cell volume=0.55±0.02 uraemic vs 0.65±0.01 control) highlighting severely impaired kidney function. However, expressions of MFN2 and DRP1 were unchanged and mitochondrial size unaltered. These findings indicate that under basal conditions mitochondrial dynamics are conserved at this stage of UCM.
- CARDIAC PROCEDURES AND THERAPY
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