Mitochondria and Endothelial Function

Kluge, Matthew A.; Fetterman, Jessica L.; Vita, Joseph A.

doi:10.1161/circresaha.111.300233

Cited by 407 publications

(409 citation statements)

References 220 publications

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“…Mfn2 is robustly expressed in muscle cells and its insufficiency has been associated with the fragmentation of the mitochondrial network, which is essential for the normal mitochondrial function (14). Inhibition of mitochondrial fission has been shown to inhibit muscle loss during fasting (11,15). In addition, downregulation of Mfn2 has been observed in the muscle of obese and non-obese type 2 diabetic subjects (16,17), and decreased mRNA expression levels of Mfn2 were observed in the skeletal muscle of tumor-bearing mice with severe cachexia (11).…”

Section: Introductionmentioning

confidence: 99%

Mitofusin-2 prevents skeletal muscle wasting in cancer cachexia

Zhang

Jiang

et al. 2016

Oncology Letters

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Abstract. Cancer cachexia remains a leading cause of morbidity and mortality worldwide, despite extensive research and clinical trials. The prominent clinical feature of cancer cachexia is the continuous loss of skeletal muscle that cannot be fully reversed by conventional nutritional support, and that leads to progressive functional impairment. The mechanism underlying muscle loss in patients with cachexia is poorly understood. The present study analyzed 21 cancer patients with or without cachexia, and demonstrated that mitofusin-2 (Mfn2) was downregulated in the rectus abdominis of patients with cachexia, which was associated with body weight loss. In vitro cell experiments indicated that loss of Mfn2 was associated with atrophy of the C2C12 mouse myoblast cell line. Furthermore, in vivo animal experiments demonstrated that cachexia decreased gastrocnemius muscle mass and Mfn2 expression, and overexpression of Mfn2 in gastrocnemius muscle was able to partially attenuate cachexia-induced gastrocnemius muscle loss. The results of the present study suggested that Mfn2 is involved in cachexia-induced muscle loss and may serve as a potential target for therapy of cachexia. IntroductionCachexia, which is the loss of body mass that cannot be reversed by nutrition, is frequently observed in patients with cancer. Cancer cachexia is a leading cause of morbidity and mortality worldwide (1). The prominent clinical feature of cancer cachexia is the continuous loss of skeletal muscle that cannot be fully reversed by conventional nutritional support, leading to progressive functional impairment (2,3). The skeletal muscle loss is associated with a reduced quality of life, as well as poor survival (4). The pathophysiology of cancer cachexia is characterized by a negative protein and energy balance (5); however, the underlying mechanism remains largely unknown. Previous studies have demonstrated that numerous signaling molecules and transcription factors are involved in the regulation of skeletal muscle mass (6,7).Mitochondrial function is crucial for the maintenance of the skeletal muscle (8). It has been demonstrated that suppression of mitochondrial function is sufficient to cause muscle wasting in adult animals (8). Mitochondrial function requires the coordination of mitochondrial fusion and fission processes that are referred to as mitochondrial dynamics (9,10). A system of pro-fusion and pro-fission proteins regulates mitochondrial morphology and subcellular localization (9,10). The fusion proteins mitofusin-1 (Mfn1) and mitofusin-2 (Mfn2) promote mitochondrial elongation and activity (11). As a major determinant of the fusion process, Mfn2 is a large GTPase that is integral to the mitochondrial outer membrane (12). It is essential for mitochondrial fusion during embryonic development and neuronal differentiation (13). In humans, mutations in the Mfn2 locus have been associated with numerous diseases, including Charcot-Marie-Tooth type 2A neuropathy, diabetes and Alzheimer's disease (14). Mfn2 is robustly expressed in mus...

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Section: Introductionmentioning

confidence: 99%

Mitofusin-2 prevents skeletal muscle wasting in cancer cachexia

Zhang

Jiang

et al. 2016

Oncology Letters

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“…8 Altering the mitochondrial membrane potential (MMP) may activate ROS production by modulating the activity of complexes I (CI) and III (CIII). 9 Therefore, in addition to their role as the cellular powerhouse, mitochondria represent promising therapeutic targets for atherosclerosis. 10 On the basis of emerging research, rather than directly eliminating all ROS, pharmacological interventions targeting specific factors in mitochondria or selectively inhibiting pathological ROS signaling cascades have been suggested to alleviate mitochondrial dysfunction and Abstract-Coronary heart disease arising from atherosclerosis is a leading cause of cardiogenic death worldwide.…”

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confidence: 99%

Ameliorating Endothelial Mitochondrial Dysfunction Restores Coronary Function via Transient Receptor Potential Vanilloid 1–Mediated Protein Kinase A/Uncoupling Protein 2 Pathway

Xiong

Wang

et al. 2016

Hypertension

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“…Most probably direct stimulation of insulin receptors and IGF receptors results in beneficial effects on neurofilament synthesis (involved in impulse conduction in the axon), protects the neuron from apoptosis induced by hyperglycaemia, and improves optimal mitochondrial function. Mitochondria are the source of most adenosine triphosphate (ATP), which is the source of energy for highly metabolically active neurons [17,18].…”

Section: Prace Oryginalnementioning

confidence: 99%