Resolution of Mitochondrial Oxidative Stress Rescues Coronary Collateral Growth in Zucker Obese Fatty Rats

Pung, Yuh Fen; Ročić, Petra; Murphy, Michael P.; Smith, Robin A.J.; Hafemeister, Jennifer L; Ohanyan, Vahagn; Guarini, G; Yin, Liya; Chilian, William M.

doi:10.1161/atvbaha.111.241802

Cited by 59 publications

(51 citation statements)

References 52 publications

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“…Previously, in a model of Zucker obese fatty (ZOF) rats with insulin resistance and impaired endothelial function, we found that resolution of mitochondrial oxidative stress restored coronary collateral growth to levels approaching those in control lean rats (47). However, our results did not delineate the precise mechanism(s) by which mitochondrial oxidative stress exerted this negative influence.…”

Section: Mitochondria As Targets Of Oxidative Stresscontrasting

confidence: 80%

“…Also as mitochondrial function is impaired, reactive oxygen species (ROS) production by the mitochondria is increased, which can lead to fragmentation of mitochondrial DNA, further impairing mitochondrial function. dative stress improved respiration profiles and antioxidant defenses (47), which led to partial restoration of coronary collateral growth in the obese rats in response to ischemia. Taken together, these results imply that in obese rats, mitochondrial oxidative stress and the consequential impaired bioenergetic capacity of the mitochondria impairs coronary collateral growth, whereas rectification of the oxidative stress with mitochondrial-directed free radical scavengers restores coronary collateral growth in response to repetitive ischemia (Fig.…”

Section: Coronary Collateral Growth: Roles Of Ucps and Ampk Under Normentioning

confidence: 93%

“…ZOF rats are a model of the human metabolic syndrome because these rats share many of the same afflictions including obesity, insulin resistance, hyperlipidemia, hyperinsulinemia, and hyperphagia (46). As the metabolic syndrome is tightly associated with mitochondrial dysfunction, we studied mitochondrial function in ZOF rats (47). We observed higher lipid peroxide contents and oxidative stress from mitochondrial proteins isolated from the left ventricular tissues in the obese compared with lean rats.…”

Section: Coronary Collateral Growth: Roles Of Ucps and Ampk Under Normentioning

confidence: 94%

“…More specifically, in ZOF rats, mitochondria demonstrate both impaired bioenergetic capacity and a higher degree of oxidative stress (47). This compromises high-energy phosphate production, which would increase the amount of AMP, whereas that of ATP would decrease.…”

Section: Coronary Collateral Growth: Roles Of Ucps and Ampk Under Normentioning

confidence: 99%

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The role of mitochondrial bioenergetics and reactive oxygen species in coronary collateral growth

Pung

Sam

Hardwick

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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Coronary collateral growth is a process involving coordination between growth factors expressed in response to ischemia and mechanical forces. Underlying this response is proliferation of vascular smooth muscle and endothelial cells, resulting in an enlargement in the caliber of arterial-arterial anastomoses, i.e., a collateral vessel, sometimes as much as an order of magnitude. An integral element of this cell proliferation is the process known as phenotypic switching in which cells of a particular phenotype, e.g., contractile vascular smooth muscle, must change their phenotype to proliferate. Phenotypic switching requires that protein synthesis occurs and different kinase signaling pathways become activated, necessitating energy to make the switch. Moreover, kinases, using ATP to phosphorylate their targets, have an energy requirement themselves. Mitochondria play a key role in the energy production that enables phenotypic switching, but under conditions where mitochondrial energy production is constrained, e.g., mitochondrial oxidative stress, this switch is impaired. In addition, we discuss the potential importance of uncoupling proteins as modulators of mitochondrial reactive oxygen species production and bioenergetics, as well as the role of AMP kinase as an energy sensor upstream of mammalian target of rapamycin, the master regulator of protein synthesis.angiogenesis; arteriogenesis; redox-dependent signaling; mitochondria THIS ARTICLE is part of a collection on Mitochondria in Cardiovascular Physiology and Disease. Other articles appearing in this collection, as well as a full archive of all collections, can be found online at http://ajpheart.physiology.org/.

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Section: Mitochondria As Targets Of Oxidative Stresscontrasting

confidence: 80%

Section: Coronary Collateral Growth: Roles Of Ucps and Ampk Under Normentioning

confidence: 93%

Section: Coronary Collateral Growth: Roles Of Ucps and Ampk Under Normentioning

confidence: 94%

Section: Coronary Collateral Growth: Roles Of Ucps and Ampk Under Normentioning

confidence: 99%

See 2 more Smart Citations

The role of mitochondrial bioenergetics and reactive oxygen species in coronary collateral growth

Pung

Sam

Hardwick

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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“…Given that MitoQ is generally adsorbed to the IMM, and the fact that its linker chain enables the penetration of the active antioxidant form, ubiquinol, deep into the membrane core, this molecule is believed to be effective as an antioxidant against mitochondrial lipid peroxidation (144, 294). The reactivity of MitoQ 10 toward O 2 -and other O 2 radicals has been studied in detail (188 (301) sepsis (180,373) diabetes, metabolic diseases, and obesity (38,199,252) ethanol-induced micro-and macrohepatosteatosis (39) neurodegeneration (342) Chronic hepatitis in HCV-infected patients (296) Cationic plastoquinone derivatives…”

Section: B Targeted Mitochondrial Deliverymentioning

confidence: 99%

Molecular Strategies for Targeting Antioxidants to Mitochondria: Therapeutic Implications

Apostolova

Víctor

2015

Antioxidants & Redox Signaling

235

147

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Mitochondrial function and specifically its implication in cellular redox/oxidative balance is fundamental in controlling the life and death of cells, and has been implicated in a wide range of human pathologies. In this context, mitochondrial therapeutics, particularly those involving mitochondria-targeted antioxidants, have attracted increasing interest as potentially effective therapies for several human diseases. For the past 10 years, great progress has been made in the development and functional testing of molecules that specifically target mitochondria, and there has been special focus on compounds with antioxidant properties. In this review, we will discuss several such strategies, including molecules conjugated with lipophilic cations (e.g., triphenylphosphonium) or rhodamine, conjugates of plant alkaloids, amino-acid-and peptide-based compounds, and liposomes. This area has several major challenges that need to be confronted. Apart from antioxidants and other redox active molecules, current research aims at developing compounds that are capable of modulating other mitochondria-controlled processes, such as apoptosis and autophagy. Multiple chemically different molecular strategies have been developed as delivery tools that offer broad opportunities for mitochondrial manipulation. Additional studies, and particularly in vivo approaches under physiologically relevant conditions, are necessary to confirm the clinical usefulness of these molecules. Antioxid. Redox Signal. 22, 686-729.

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Perspectives and Potential Applications of Mitochondria‐Targeted Antioxidants in Cardiometabolic Diseases and Type 2 Diabetes

Rocha

Apostolova

Herance

et al. 2013

Medicinal Research Reviews

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There is abundant evidence to suggest that mitochondrial dysfunction is a main cause of insulin resistance and related cardiometabolic comorbidities. On the other hand, insulin resistance is one of the main characteristics of type 2 diabetes, obesity, and metabolic syndrome. Lipid and glucose metabolism require mitochondria to generate energy, and when O 2 consumption is low due to inefficient nutrient oxidation, there is an increase in reactive oxygen species, which can impair different types of molecules, including DNA, lipids, proteins, and carbohydrates, thereby inducing proinflammatory processes. Factors which contribute to mitochondrial dysfunction, such as mitochondrial biogenesis and genetics, can also lead to insulin resistance in different insulin-target tissues, and its association with mitochondrial dysfunction can culminate in the development of cardiovascular diseases. In this context, therapies that improve mitochondrial function may also improve insulin resistance. This review explains mechanisms of mitochondrial function related to the pathological effects of insulin resistance in different tissues. The pathogenesis of cardiometabolic diseases will be explained from a mitochondrial perspective * These authors have contributed equally to this work.

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Resolution of Mitochondrial Oxidative Stress Rescues Coronary Collateral Growth in Zucker Obese Fatty Rats

Cited by 59 publications

References 52 publications

The role of mitochondrial bioenergetics and reactive oxygen species in coronary collateral growth

The role of mitochondrial bioenergetics and reactive oxygen species in coronary collateral growth

Molecular Strategies for Targeting Antioxidants to Mitochondria: Therapeutic Implications

Perspectives and Potential Applications of Mitochondria‐Targeted Antioxidants in Cardiometabolic Diseases and Type 2 Diabetes

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