Berru 2019 Sci Rep
|Berru FN, Gray SE, Thome T, Kumar RA, Salyers ZR, Coleman M, Dennis Le, O'Malley K, Ferreira LF, Berceli SA, Scali ST, Ryan TE (2019) Chronic kidney disease exacerbates ischemic limb myopathy in mice via altered mitochondrial energetics. Sci Rep 9:15547.|
Abstract: Chronic kidney disease (CKD) substantially increases the severity of peripheral arterial disease (PAD) symptomology, however, the biological mechanisms remain unclear. The objective herein was to determine the impact of CKD on PAD pathology in mice. C57BL6/J mice were subjected to a diet-induced model of CKD by delivery of adenine for six weeks. CKD was confirmed by measurements of glomerular filtration rate, blood urea nitrogen, and kidney histopathology. Mice with CKD displayed lower muscle force production and greater ischemic lesions in the tibialis anterior muscle (78.1 ± 14.5% vs. 2.5 ± 0.5% in control mice, P < 0.0001, N = 5-10/group) and decreased myofiber size (1661 ± 134 μm2 vs. 2221 ± 100 μm2 in control mice, P < 0.01, N = 5-10/group). This skeletal myopathy occurred despite normal capillary density (516 ± 59 vs. 466 ± 45 capillaries/20x field of view) and limb perfusion. CKD mice displayed a ~50-65% reduction in muscle mitochondrial respiratory capacity in ischemic muscle, whereas control mice had normal mitochondrial function. Hydrogen peroxide emission was modestly higher in the ischemic muscle of CKD mice, which coincided with decreased oxidant buffering. Exposure of cultured myotubes to CKD serum resulted in myotube atrophy and elevated oxidative stress, which were attenuated by mitochondrial-targeted therapies. Taken together, these findings suggest that mitochondrial impairments caused by CKD contribute to the exacerbation of ischemic pathology.
Labels: MiParea: Respiration Pathology: Myopathy, Other Stress:Ischemia-reperfusion Organism: Mouse Tissue;cell: Skeletal muscle Preparation: Permeabilized tissue
Coupling state: LEAK, OXPHOS Pathway: N, S, CIV, NS, ROX HRR: Oxygraph-2k