Berru 2019 Sci Rep: Difference between revisions
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|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 (78.1โยฑโ14.5% vs. 2.5โยฑโ0.5% in control mice, Pโ<โ0.0001, Nโ=โ5-10/group) and decreased myofiber size (1661โยฑโ134โฮผm<sup>2</sup> vs. 2221โยฑโ100โฮผm<sup>2</sup> in control mice, Pโ<โ0.01, Nโ=โ5-10/group). This skeletal myopathy occurred despite normal capillary density (516โยฑโ59 vs. 466โยฑโ45 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. | |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 (78.1โยฑโ14.5% vs. 2.5โยฑโ0.5% in control mice, Pโ<โ0.0001, Nโ=โ5-10/group) and decreased myofiber size (1661โยฑโ134โฮผm<sup>2</sup> vs. 2221โยฑโ100โฮผm<sup>2</sup> in control mice, Pโ<โ0.01, Nโ=โ5-10/group). This skeletal myopathy occurred despite normal capillary density (516โยฑโ59 vs. 466โยฑโ45 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. | ||
|editor=[[Plangger M]], | |editor=[[Plangger M]], | ||
|mipnetlab=US FL Gainesville Ryan TE | |||
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{{Labeling | {{Labeling |
Revision as of 17:17, 4 November 2019
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. |
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) Sci Rep
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 (78.1โยฑโ14.5% vs. 2.5โยฑโ0.5% in control mice, Pโ<โ0.0001, Nโ=โ5-10/group) and decreased myofiber size (1661โยฑโ134โฮผm2 vs. 2221โยฑโ100โฮผm2 in control mice, Pโ<โ0.01, Nโ=โ5-10/group). This skeletal myopathy occurred despite normal capillary density (516โยฑโ59 vs. 466โยฑโ45 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.
โข Bioblast editor: Plangger M โข O2k-Network Lab: US FL Gainesville Ryan TE
Labels: MiParea: Respiration
Pathology: Myopathy, Other
Stress:Ischemia-reperfusion
Organism: Mouse
Coupling state: LEAK, OXPHOS
Pathway: N, S, CIV, NS, ROX
HRR: Oxygraph-2k
Labels, 2019-11