Mitochondria: A mirror into cellular dysfunction in heart disease

White, Melanie Y.; Edwards, A.; Cordwell, Stuart J.; Eyk, Jennifer E. Van

doi:10.1002/prca.200780135

Cited by 24 publications

(17 citation statements)

References 233 publications

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“…Also, the discovery that acute and chronic stress in the cells leads to structural and functional impairments of mitochondria has redefined the role of these organelles in disease etiology and thus, alterations in mitochondrial function are currently considered to play key roles in the development of human disease [42,43]. Mitochondrial dysfunction triggers signalling cascades for cell necrosis and apoptosis, and leads to organ failure.…”

Section: Oxidative Stress and Mitochondrial Dysfunctionmentioning

confidence: 99%

Oxidative Stress and Endothelial Dysfunction in Cardiovascular Disease: Mitochondria-Targeted Therapeutics

Rocha

Apostolova²,

Hernández‐Mijares³

et al. 2010

CMC

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Functional impairment of endothelial activity (endothelial dysfunction) precedes the development of cardiovascular diseases (CVD). This condition is a result of a reduced bioavailability of nitric oxide (NO), a well known vasodilator, which is mainly due to increased NO degradation caused by its reaction with reactive oxygen species (ROS). Although there are several conditions that contribute independently to endothelial dysfunction, such as hyperglycemia, insulin resistance, hyperinsulinemia and dyslipidemia, increased oxidative stress seems to play a key role. In addition to their original pharmacological properties, drugs used clinically at present, including anti-hypertension reagents, angiotensin receptor blockers and anti-hyperlipidemic reagents such as statins, protect various organs via anti-oxidative stress mechanisms. Moreover, some substances with antioxidant properties, such as vitamin C or vitamin E, have been used to eradicate the oxidative stress associated with CVD. The results of the clinical trials employing anti-oxidative stress reagents in patients with CVD are contradictory, which could be a result of inadequate study design or selected targets. This review considers the process of endothelial dysfunction and CVD from a mitochondrial perspective and evaluates strategies currently under development for the targeted delivery of antioxidants or NO to mitochondria. It endorses the idea that selectively targeting specific antioxidants and NO donors to mitochondria is an effective strategy for modulating mitochondrial respiration and ROS production and protecting mitochondria against oxidative stress.

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Section: Oxidative Stress and Mitochondrial Dysfunctionmentioning

confidence: 99%

Oxidative Stress and Endothelial Dysfunction in Cardiovascular Disease: Mitochondria-Targeted Therapeutics

Rocha

Apostolova²,

Hernández‐Mijares³

et al. 2010

CMC

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“…Clinical markers of myocardial necrosis and dysfunction include blood pressure, heart rate and electrocardiographic (ECG) changes and left ventricular (LV) dysfunction accompanied with increased serum levels of cardiac-specific proteins. Cardiac troponins are frequently associated with myocardial infarction and inflammation-related proteins at elevated levels with heart attack [2]. The animal model of isoproterenol-induced myocardial infarction presents an important endorsed technique for studying the effects of several potential cardioprotective bioactive compounds [3].…”

Section: Introductionmentioning

confidence: 99%

Protective Effect of Hydroxytyrosol Against Cardiac Remodeling After Isoproterenol-Induced Myocardial Infarction in Rat

Mnafgui

Hajji²,

Derbali³

et al. 2015

Cardiovasc Toxicol

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The present study aimed to investigate the cardioprotective effect of hydroxytyrosol (HT) against isoproterenol-induced myocardial infarction in rats. Male rats were randomly divided into four groups, control, isoproterenol (Isop) and pretreated animals with HT in two different doses (2 and 5 mg/kg) orally for 7 days and intoxicated with isoproterenol (Isop + HT1) and (Isop + HT2) groups. Myocardial infarction in rats was induced subcutaneously by isoproterenol (100 mg/kg, s.c.) at an interval of 24 h on 6th and 7th day. On 8th day, electrocardiographic (ECG) pattern, gravimetric and biochemical parameters were assessed. Isoproterenol exhibited changes in ECG pattern, including significant ST-segment elevation and increase in the serum troponin-T level by 317 % as compared to control rats. Moreover, cardiac injury markers (creatine kinase-MB, lactate dehydrogenase, alanine aminotransferase) underwent a notable rise in serum of infarcted animals. Else, a disturbance in lipids profile and significant increase in lipase and angiotensin-converting enzyme (ACE) activities and heart weight ratio were observed in isoproterenol group. However, pre- and co-treatment with HT (2 and 5 mg/kg) improved the myocardium injury, restored the hemodynamic function and inhibited the ACE activity that prevent cardiac hypertrophy and remodeling. Overall, these findings demonstrated that HT exerted a potent cardioprotective effect against isoproterenol-induced myocardial infarction.

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“…As heart tissue has a high energy demand, it is not surprising that mitochondria contribute about 40% of the total cellular volume of cardiomyocytes [30]. Approximately 90% of energy is supplied by these organelles [31].…”

Section: Introductionmentioning

confidence: 99%

Radiation–Induced Signaling Results in Mitochondrial Impairment in Mouse Heart at 4 Weeks after Exposure to X-Rays

et al. 2011

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BackroundRadiation therapy treatment of breast cancer, Hodgkin's disease or childhood cancers expose the heart to high local radiation doses, causing an increased risk of cardiovascular disease in the survivors decades after the treatment. The mechanisms that underlie the radiation damage remain poorly understood so far. Previous data show that impairment of mitochondrial oxidative metabolism is directly linked to the development of cardiovascular disease.Methodology/Principal findingsIn this study, the radiation-induced in vivo effects on cardiac mitochondrial proteome and function were investigated. C57BL/6N mice were exposed to local irradiation of the heart with doses of 0.2 Gy or 2 Gy (X-ray, 200 kV) at the age of eight weeks, the control mice were sham-irradiated. After four weeks the cardiac mitochondria were isolated and tested for proteomic and functional alterations. Two complementary proteomics approaches using both peptide and protein quantification strategies showed radiation-induced deregulation of 25 proteins in total. Three main biological categories were affected: the oxidative phophorylation, the pyruvate metabolism, and the cytoskeletal structure. The mitochondria exposed to high-dose irradiation showed functional impairment reflected as partial deactivation of Complex I (32%) and Complex III (11%), decreased succinate-driven respiratory capacity (13%), increased level of reactive oxygen species and enhanced oxidation of mitochondrial proteins. The changes in the pyruvate metabolism and structural proteins were seen with both low and high radiation doses.Conclusion/SignificanceThis is the first study showing the biological alterations in the murine heart mitochondria several weeks after the exposure to low- and high-dose of ionizing radiation. Our results show that doses, equivalent to a single dose in radiotherapy, cause long-lasting changes in mitochondrial oxidative metabolism and mitochondria-associated cytoskeleton. This prompts us to propose that these first pathological changes lead to an increased risk of cardiovascular disease after radiation exposure.

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Mitochondria: A mirror into cellular dysfunction in heart disease

Cited by 24 publications

References 233 publications

Oxidative Stress and Endothelial Dysfunction in Cardiovascular Disease: Mitochondria-Targeted Therapeutics

Oxidative Stress and Endothelial Dysfunction in Cardiovascular Disease: Mitochondria-Targeted Therapeutics

Protective Effect of Hydroxytyrosol Against Cardiac Remodeling After Isoproterenol-Induced Myocardial Infarction in Rat

Radiation–Induced Signaling Results in Mitochondrial Impairment in Mouse Heart at 4 Weeks after Exposure to X-Rays

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