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Chronic kidney disease exacerbates ischemic limb myopathy in mice via altered mitochondrial energetics
by
Salyers, Zachary R.
, Scali, Salvatore T.
, O’Malley, Kerri
, Ferreira, Leonardo F.
, Thome, Trace
, Gray, Sarah E.
, Kumar, Ravi A.
, Ryan, Terence E.
, Berru, Fabian N.
, Coleman, Madeline
, Berceli, Scott A.
, Dennis Le
in
14
/ 14/34
/ 64/60
/ 692/4019/592/75/593/1920
/ 692/4022/1585/104
/ Adenine
/ Animals
/ Atrophy
/ Capillaries
/ Female
/ Glomerular filtration rate
/ Hindlimb - blood supply
/ Hindlimb - metabolism
/ Hindlimb - pathology
/ Histopathology
/ Humanities and Social Sciences
/ Humans
/ Hydrogen peroxide
/ Ischemia
/ Ischemia - metabolism
/ Ischemia - pathology
/ Kidney diseases
/ Kidneys
/ Male
/ Mice
/ Mitochondria
/ Mitochondria, Muscle - metabolism
/ Mitochondria, Muscle - pathology
/ multidisciplinary
/ Muscle, Skeletal - blood supply
/ Muscle, Skeletal - metabolism
/ Muscle, Skeletal - pathology
/ Muscular Diseases - metabolism
/ Muscular Diseases - pathology
/ Myopathy
/ Myotubes
/ Oxidative Stress
/ Oxidizing agents
/ Pathology
/ Perfusion
/ Renal Insufficiency, Chronic - metabolism
/ Renal Insufficiency, Chronic - pathology
/ Science
/ Science (multidisciplinary)
/ Skeletal muscle
/ Tibialis anterior muscle
/ Urea
2019
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Chronic kidney disease exacerbates ischemic limb myopathy in mice via altered mitochondrial energetics
by
Salyers, Zachary R.
, Scali, Salvatore T.
, O’Malley, Kerri
, Ferreira, Leonardo F.
, Thome, Trace
, Gray, Sarah E.
, Kumar, Ravi A.
, Ryan, Terence E.
, Berru, Fabian N.
, Coleman, Madeline
, Berceli, Scott A.
, Dennis Le
in
14
/ 14/34
/ 64/60
/ 692/4019/592/75/593/1920
/ 692/4022/1585/104
/ Adenine
/ Animals
/ Atrophy
/ Capillaries
/ Female
/ Glomerular filtration rate
/ Hindlimb - blood supply
/ Hindlimb - metabolism
/ Hindlimb - pathology
/ Histopathology
/ Humanities and Social Sciences
/ Humans
/ Hydrogen peroxide
/ Ischemia
/ Ischemia - metabolism
/ Ischemia - pathology
/ Kidney diseases
/ Kidneys
/ Male
/ Mice
/ Mitochondria
/ Mitochondria, Muscle - metabolism
/ Mitochondria, Muscle - pathology
/ multidisciplinary
/ Muscle, Skeletal - blood supply
/ Muscle, Skeletal - metabolism
/ Muscle, Skeletal - pathology
/ Muscular Diseases - metabolism
/ Muscular Diseases - pathology
/ Myopathy
/ Myotubes
/ Oxidative Stress
/ Oxidizing agents
/ Pathology
/ Perfusion
/ Renal Insufficiency, Chronic - metabolism
/ Renal Insufficiency, Chronic - pathology
/ Science
/ Science (multidisciplinary)
/ Skeletal muscle
/ Tibialis anterior muscle
/ Urea
2019
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Chronic kidney disease exacerbates ischemic limb myopathy in mice via altered mitochondrial energetics
by
Salyers, Zachary R.
, Scali, Salvatore T.
, O’Malley, Kerri
, Ferreira, Leonardo F.
, Thome, Trace
, Gray, Sarah E.
, Kumar, Ravi A.
, Ryan, Terence E.
, Berru, Fabian N.
, Coleman, Madeline
, Berceli, Scott A.
, Dennis Le
in
14
/ 14/34
/ 64/60
/ 692/4019/592/75/593/1920
/ 692/4022/1585/104
/ Adenine
/ Animals
/ Atrophy
/ Capillaries
/ Female
/ Glomerular filtration rate
/ Hindlimb - blood supply
/ Hindlimb - metabolism
/ Hindlimb - pathology
/ Histopathology
/ Humanities and Social Sciences
/ Humans
/ Hydrogen peroxide
/ Ischemia
/ Ischemia - metabolism
/ Ischemia - pathology
/ Kidney diseases
/ Kidneys
/ Male
/ Mice
/ Mitochondria
/ Mitochondria, Muscle - metabolism
/ Mitochondria, Muscle - pathology
/ multidisciplinary
/ Muscle, Skeletal - blood supply
/ Muscle, Skeletal - metabolism
/ Muscle, Skeletal - pathology
/ Muscular Diseases - metabolism
/ Muscular Diseases - pathology
/ Myopathy
/ Myotubes
/ Oxidative Stress
/ Oxidizing agents
/ Pathology
/ Perfusion
/ Renal Insufficiency, Chronic - metabolism
/ Renal Insufficiency, Chronic - pathology
/ Science
/ Science (multidisciplinary)
/ Skeletal muscle
/ Tibialis anterior muscle
/ Urea
2019
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Chronic kidney disease exacerbates ischemic limb myopathy in mice via altered mitochondrial energetics
Journal Article
Chronic kidney disease exacerbates ischemic limb myopathy in mice via altered mitochondrial energetics
2019
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Overview
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 μm
2
vs. 2221 ± 100 μm
2
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 14/34
/ 64/60
/ Adenine
/ Animals
/ Atrophy
/ Female
/ Humanities and Social Sciences
/ Humans
/ Ischemia
/ Kidneys
/ Male
/ Mice
/ Mitochondria, Muscle - metabolism
/ Mitochondria, Muscle - pathology
/ Muscle, Skeletal - blood supply
/ Muscle, Skeletal - metabolism
/ Muscle, Skeletal - pathology
/ Muscular Diseases - metabolism
/ Muscular Diseases - pathology
/ Myopathy
/ Myotubes
/ Renal Insufficiency, Chronic - metabolism
/ Renal Insufficiency, Chronic - pathology
/ Science
/ Urea
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