Skeletal Muscle Mitochondrial Dysfunction and Oxidative Stress in Peripheral Arterial Disease: A Unifying Mechanism and Therapeutic Target
Peripheral artery disease (PAD) is caused by atherosclerosis in the lower extremities, which leads to a spectrum of life-altering symptomatology, including claudication, ischemic rest pain, and gangrene requiring limb amputation. Current treatments for PAD are focused primarily on re-establishing bl...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-12-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/9/12/1304 |
| _version_ | 1797544126738071552 |
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| author | Kyoungrae Kim Erik M. Anderson Salvatore T. Scali Terence E. Ryan |
| author_facet | Kyoungrae Kim Erik M. Anderson Salvatore T. Scali Terence E. Ryan |
| author_sort | Kyoungrae Kim |
| collection | DOAJ |
| description | Peripheral artery disease (PAD) is caused by atherosclerosis in the lower extremities, which leads to a spectrum of life-altering symptomatology, including claudication, ischemic rest pain, and gangrene requiring limb amputation. Current treatments for PAD are focused primarily on re-establishing blood flow to the ischemic tissue, implying that blood flow is the decisive factor that determines whether or not the tissue survives. Unfortunately, failure rates of endovascular and revascularization procedures remain unacceptably high and numerous cell- and gene-based vascular therapies have failed to demonstrate efficacy in clinical trials. The low success of vascular-focused therapies implies that non-vascular tissues, such as skeletal muscle and oxidative stress, may substantially contribute to PAD pathobiology. Clues toward the importance of skeletal muscle in PAD pathobiology stem from clinical observations that muscle function is a strong predictor of mortality. Mitochondrial impairments in muscle have been documented in PAD patients, although its potential role in clinical pathology is incompletely understood. In this review, we discuss the underlying mechanisms causing mitochondrial dysfunction in ischemic skeletal muscle, including causal evidence in rodent studies, and highlight emerging mitochondrial-targeted therapies that have potential to improve PAD outcomes. Particularly, we will analyze literature data on reactive oxygen species production and potential counteracting endogenous and exogenous antioxidants. |
| first_indexed | 2024-03-10T13:55:57Z |
| format | Article |
| id | doaj.art-302e3a276f124bd48f86efb4a05863d2 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T13:55:57Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-302e3a276f124bd48f86efb4a05863d22023-11-21T01:35:26ZengMDPI AGAntioxidants2076-39212020-12-01912130410.3390/antiox9121304Skeletal Muscle Mitochondrial Dysfunction and Oxidative Stress in Peripheral Arterial Disease: A Unifying Mechanism and Therapeutic TargetKyoungrae Kim0Erik M. Anderson1Salvatore T. Scali2Terence E. Ryan3Department of Applied Physiology & Kinesiology, University of Florida, Gainesville, FL 32611, USADivision of Vascular Surgery and Endovascular Therapy, University of Florida, Gainesville, FL 32611, USADivision of Vascular Surgery and Endovascular Therapy, University of Florida, Gainesville, FL 32611, USADepartment of Applied Physiology & Kinesiology, University of Florida, Gainesville, FL 32611, USAPeripheral artery disease (PAD) is caused by atherosclerosis in the lower extremities, which leads to a spectrum of life-altering symptomatology, including claudication, ischemic rest pain, and gangrene requiring limb amputation. Current treatments for PAD are focused primarily on re-establishing blood flow to the ischemic tissue, implying that blood flow is the decisive factor that determines whether or not the tissue survives. Unfortunately, failure rates of endovascular and revascularization procedures remain unacceptably high and numerous cell- and gene-based vascular therapies have failed to demonstrate efficacy in clinical trials. The low success of vascular-focused therapies implies that non-vascular tissues, such as skeletal muscle and oxidative stress, may substantially contribute to PAD pathobiology. Clues toward the importance of skeletal muscle in PAD pathobiology stem from clinical observations that muscle function is a strong predictor of mortality. Mitochondrial impairments in muscle have been documented in PAD patients, although its potential role in clinical pathology is incompletely understood. In this review, we discuss the underlying mechanisms causing mitochondrial dysfunction in ischemic skeletal muscle, including causal evidence in rodent studies, and highlight emerging mitochondrial-targeted therapies that have potential to improve PAD outcomes. Particularly, we will analyze literature data on reactive oxygen species production and potential counteracting endogenous and exogenous antioxidants.https://www.mdpi.com/2076-3921/9/12/1304myopathyperipheral vascular diseasebioenergeticsischemiareactive oxygen species |
| spellingShingle | Kyoungrae Kim Erik M. Anderson Salvatore T. Scali Terence E. Ryan Skeletal Muscle Mitochondrial Dysfunction and Oxidative Stress in Peripheral Arterial Disease: A Unifying Mechanism and Therapeutic Target Antioxidants myopathy peripheral vascular disease bioenergetics ischemia reactive oxygen species |
| title | Skeletal Muscle Mitochondrial Dysfunction and Oxidative Stress in Peripheral Arterial Disease: A Unifying Mechanism and Therapeutic Target |
| title_full | Skeletal Muscle Mitochondrial Dysfunction and Oxidative Stress in Peripheral Arterial Disease: A Unifying Mechanism and Therapeutic Target |
| title_fullStr | Skeletal Muscle Mitochondrial Dysfunction and Oxidative Stress in Peripheral Arterial Disease: A Unifying Mechanism and Therapeutic Target |
| title_full_unstemmed | Skeletal Muscle Mitochondrial Dysfunction and Oxidative Stress in Peripheral Arterial Disease: A Unifying Mechanism and Therapeutic Target |
| title_short | Skeletal Muscle Mitochondrial Dysfunction and Oxidative Stress in Peripheral Arterial Disease: A Unifying Mechanism and Therapeutic Target |
| title_sort | skeletal muscle mitochondrial dysfunction and oxidative stress in peripheral arterial disease a unifying mechanism and therapeutic target |
| topic | myopathy peripheral vascular disease bioenergetics ischemia reactive oxygen species |
| url | https://www.mdpi.com/2076-3921/9/12/1304 |
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