Skeletal muscle mitochondrial remodeling in heart failure: An update on mechanisms and therapeutic opportunities
Patients with heart failure (HF) usually present with skeletal muscle diseases of varying severity, ranging from early fatigue on exercise to sarcopenia, sarcopenic obesity or cachexia, and frailty, which are significant predictors of HF prognosis. Abnormal mitochondrial metabolism has been identifi...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-11-01
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| Series: | Biomedicine & Pharmacotherapy |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332222012227 |
| _version_ | 1797986183587823616 |
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| author | Jiayu Lv Yumeng Li Shuqing Shi Xia Xu Huaqin Wu Bingxuan Zhang Qingqiao Song |
| author_facet | Jiayu Lv Yumeng Li Shuqing Shi Xia Xu Huaqin Wu Bingxuan Zhang Qingqiao Song |
| author_sort | Jiayu Lv |
| collection | DOAJ |
| description | Patients with heart failure (HF) usually present with skeletal muscle diseases of varying severity, ranging from early fatigue on exercise to sarcopenia, sarcopenic obesity or cachexia, and frailty, which are significant predictors of HF prognosis. Abnormal mitochondrial metabolism has been identified as one of the earliest signs of skeletal muscle injury in HF and is associated with pathological alterations in muscle, manifested as muscle wasting, myocyte atrophy and apoptosis, fiber type shift, impaired contractile coupling, and muscle fat infiltration. In this review, we update the evidence for skeletal muscle mitochondrial remodeling in HF patients or animal models, including the impairments in mitochondrial ultrastructure, oxidative metabolism, electron transport chain (ETC), phosphorylation apparatus, phosphotransfer system, and quality control. We also focus on molecular regulatory mechanisms upstream of mitochondria, including circulating factors (e.g., RAAS, TNF-α IL-6, IGF-1, GH, ghrelin, adiponectin, NO) and molecular signals within myocytes (e.g., PGC-1α, PPARs, AMPK, SIRT1/3, ROS, and MuRF1). Besides the therapies targeting the signaling pathways mentioned above, such as AdipoRon and elamipretide, we further summarize other potential pharmacological approaches like inhibitors of sodium-glucose cotransporter 2 (SGLT2) and dipeptidyl peptidase-4 (DPP-4), as well as some natural products, which may have the beneficial effects on improving the skeletal muscle mitochondrial function of HF. Targeting myocyte mitochondrial biogenesis, oxidative metabolism, oxidative phosphorylation, and reduction of oxidative stress injury are promising future opportunities for the prevention and management of skeletal muscle myopathy in HF. |
| first_indexed | 2024-04-11T07:30:00Z |
| format | Article |
| id | doaj.art-ab7d25af35e54000b515058040a1e283 |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-04-11T07:30:00Z |
| publishDate | 2022-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-ab7d25af35e54000b515058040a1e2832022-12-22T04:36:57ZengElsevierBiomedicine & Pharmacotherapy0753-33222022-11-01155113833Skeletal muscle mitochondrial remodeling in heart failure: An update on mechanisms and therapeutic opportunitiesJiayu Lv0Yumeng Li1Shuqing Shi2Xia Xu3Huaqin Wu4Bingxuan Zhang5Qingqiao Song6Department of General Internal Medicine, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China; College of Traditional Chinese Medicine, China Academy of Chinese Medical Science, Beijing, ChinaDepartment of General Internal Medicine, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, ChinaDepartment of General Internal Medicine, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, ChinaDepartment of General Internal Medicine, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China; College of Traditional Chinese Medicine, China Academy of Chinese Medical Science, Beijing, ChinaDepartment of Cardiology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, ChinaDepartment of General Internal Medicine, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China; Corresponding authors.Department of General Internal Medicine, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China; Corresponding authors.Patients with heart failure (HF) usually present with skeletal muscle diseases of varying severity, ranging from early fatigue on exercise to sarcopenia, sarcopenic obesity or cachexia, and frailty, which are significant predictors of HF prognosis. Abnormal mitochondrial metabolism has been identified as one of the earliest signs of skeletal muscle injury in HF and is associated with pathological alterations in muscle, manifested as muscle wasting, myocyte atrophy and apoptosis, fiber type shift, impaired contractile coupling, and muscle fat infiltration. In this review, we update the evidence for skeletal muscle mitochondrial remodeling in HF patients or animal models, including the impairments in mitochondrial ultrastructure, oxidative metabolism, electron transport chain (ETC), phosphorylation apparatus, phosphotransfer system, and quality control. We also focus on molecular regulatory mechanisms upstream of mitochondria, including circulating factors (e.g., RAAS, TNF-α IL-6, IGF-1, GH, ghrelin, adiponectin, NO) and molecular signals within myocytes (e.g., PGC-1α, PPARs, AMPK, SIRT1/3, ROS, and MuRF1). Besides the therapies targeting the signaling pathways mentioned above, such as AdipoRon and elamipretide, we further summarize other potential pharmacological approaches like inhibitors of sodium-glucose cotransporter 2 (SGLT2) and dipeptidyl peptidase-4 (DPP-4), as well as some natural products, which may have the beneficial effects on improving the skeletal muscle mitochondrial function of HF. Targeting myocyte mitochondrial biogenesis, oxidative metabolism, oxidative phosphorylation, and reduction of oxidative stress injury are promising future opportunities for the prevention and management of skeletal muscle myopathy in HF.http://www.sciencedirect.com/science/article/pii/S0753332222012227Heart failureSkeletal muscleMitochondriaMolecular mechanismsPharmacological targets |
| spellingShingle | Jiayu Lv Yumeng Li Shuqing Shi Xia Xu Huaqin Wu Bingxuan Zhang Qingqiao Song Skeletal muscle mitochondrial remodeling in heart failure: An update on mechanisms and therapeutic opportunities Biomedicine & Pharmacotherapy Heart failure Skeletal muscle Mitochondria Molecular mechanisms Pharmacological targets |
| title | Skeletal muscle mitochondrial remodeling in heart failure: An update on mechanisms and therapeutic opportunities |
| title_full | Skeletal muscle mitochondrial remodeling in heart failure: An update on mechanisms and therapeutic opportunities |
| title_fullStr | Skeletal muscle mitochondrial remodeling in heart failure: An update on mechanisms and therapeutic opportunities |
| title_full_unstemmed | Skeletal muscle mitochondrial remodeling in heart failure: An update on mechanisms and therapeutic opportunities |
| title_short | Skeletal muscle mitochondrial remodeling in heart failure: An update on mechanisms and therapeutic opportunities |
| title_sort | skeletal muscle mitochondrial remodeling in heart failure an update on mechanisms and therapeutic opportunities |
| topic | Heart failure Skeletal muscle Mitochondria Molecular mechanisms Pharmacological targets |
| url | http://www.sciencedirect.com/science/article/pii/S0753332222012227 |
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