Enhanced oxidative stress in hypertrophic cardiomyopathy

Dimitrow, Paweł Petkow; Undas, Anetta; Wołkow, Paweł; Tracz, Wiesława; Dubiel, Jacek S.

doi:10.1016/s1734-1140(09)70091-x

Cited by 46 publications

(41 citation statements)

References 17 publications

(29 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been reported that systemic oxidative stress, evaluated by serum levels of 8-iso-PGF 2␣ , is enhanced in patients with HCM (10). Furthermore, oxidative damage in the right ventricular side of the septum has been shown to be increased in patients with HCM (38), which is consistent with our findings of higher myocardial TBARS in cats with HCM.…”

Section: Enhanced Mitochondrial Oxidative Stress In the Hcm Heartsupporting

confidence: 92%

Impaired cardiac mitochondrial oxidative phosphorylation and enhanced mitochondrial oxidative stress in feline hypertrophic cardiomyopathy

Christiansen

Dela

Koch

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Yokota T. Impaired cardiac mitochondrial oxidative phosphorylation and enhanced mitochondrial oxidative stress in feline hypertrophic cardiomyopathy. Am J Physiol Heart Circ Physiol 308: H1237-H1247, 2015. First published March 13, 2015; doi:10.1152/ajpheart.00727.2014.-Mitochondrial dysfunction and oxidative stress are important players in the development of various cardiovascular diseases, but their roles in hypertrophic cardiomyopathy (HCM) remain unknown. We examined whether mitochondrial oxidative phosphorylation (OXPHOS) capacity was impaired with enhanced mitochondrial oxidative stress in HCM. Cardiac and skeletal muscles were obtained from 9 domestic cats with spontaneously occurring HCM with preserved left ventricular systolic function and from 15 age-matched control cats. Mitochondrial OXPHOS capacities with nonfatty acid and fatty acid substrates in permeabilized fibers and isolated mitochondria were assessed using high-resolution respirometry. ROS release originating from isolated mitochondria was assessed by spectrofluorometry. Thiobarbituric acid-reactive substances were also measured as a marker of oxidative damage. Mitochondrial ADP-stimulated state 3 respiration with complex I-linked nonfatty acid substrates and with fatty acid substrates, respectively, was significantly lower in the hearts of HCM cats compared with control cats. Mitochondrial ROS release during state 3 with complex I-linked substrates and thiobarbituric acid-reactive substances in the heart were significantly increased in cats with HCM. In contrast, there were no significant differences in mitochondrial OXPHOS capacity, mitochondrial ROS release, and oxidative damage in skeletal muscle between groups. Mitochondrial OXPHOS capacity with both nonfatty acid substrates and fatty acid substrates was impaired with increased mitochondrial ROS release in the feline HCM heart. These findings provide new insights into the pathophysiology of HCM and support the hypothesis that restoration of the redox state in the mitochondria is beneficial in the treatment of HCM. hypertrophic cardiomyopathy; mitochondria; oxidative stress

show abstract

Section: Enhanced Mitochondrial Oxidative Stress In the Hcm Heartsupporting

confidence: 92%

Impaired cardiac mitochondrial oxidative phosphorylation and enhanced mitochondrial oxidative stress in feline hypertrophic cardiomyopathy

Christiansen

Dela

Koch

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

show abstract

“…This was associated with improved left ventricular outflow tract dimensions, suggesting a possible contribution of FD in delaying the progression of SCD cardiovascular disease. [54][55][56] We demonstrated a synergistic effect of ω-3 PUFA on both ET-1-mediated endothelial dysfunction and VCAM-1-mediated endothelial activation on aortas following H/R ( Figure 6A). Notably, FD also significantly reduced VCAM-1 expression in livers of SS mice exposed to H/R stress compared to the expression in SS-SD mice ( Figure 5).…”

Section: Discussionmentioning

confidence: 89%

Dietary -3 fatty acids protect against vasculopathy in a transgenic mouse model of sickle cell disease

et al. 2015

View full text Add to dashboard Cite

The anemia of sickle cell disease is associated with a severe inflammatory vasculopathy and endothelial dysfunction, which leads to painful and life-threatening clinical complications. Growing evidence supports the anti-inflammatory properties of ω-3 fatty acids in clinical models of endothelial dysfunction. Promising but limited studies show potential therapeutic effects of ω-3 fatty acid supplementation in sickle cell disease. Here, we treated humanized healthy and sickle cell mice for 6 weeks with ω-3 fatty acid diet (fish-oil diet). We found that a ω-3 fatty acid diet: (i) normalizes red cell membrane ω-6/ ω-3 ratio; (ii) reduces neutrophil count; (iii) decreases endothelial activation by targeting endothelin-1 and (iv) improves left ventricular outflow tract dimensions. In a hypoxia-reoxygenation model of acute vaso-occlusive crisis, a ω-3 fatty acid diet reduced systemic and local inflammation and protected against sickle cell-related end-organ injury. Using isolated aortas from sickle cell mice exposed to hypoxia-reoxygenation, we demonstrated a direct impact of a ω-3 fatty acid diet on vascular activation, inflammation, and anti-oxidant systems. Our data provide the rationale for ω-3 dietary supplementation as a therapeutic intervention to reduce vascular dysfunction in sickle cell disease. ABSTRACTmice. 16,17 The animal protocol was approved by the Animal Care and Use Committee of the University of Verona (CIRSAL). Twomonth old animals were fed for 6 weeks with either the standard AIN-93M purified rodent diet (soy-diet with n6/n3 ratio of 8:1 -Dyets Inc., Bethlehem, PA, USA), containing 140 g/kg casein, 1.8 g/kg L-cystine, 100 g/kg sucrose, 465.9 g/kg cornstarch, 155 g/kg dextrose, 40 g/kg soybean oil, 0.8 mg/kg t-butylhydroquinone, 50 g/kg cellulose, 35 g/kg mineral mix, 10 g/kg vitamin mix, and 2.5 g/kg choline bitartrate 18 or the ω-3 FD, an AIN-93M-based purified rodent diet in which all of the calories provided by fat (10%) are replaced by 7.9% from HCO and 2.1% from ω-3 oil (Dyets Inc., Bethlehem, PA, USA). At the end of the 6 weeks of FD supplementation, animals were anesthetized with isofluorane, and whole blood was collected from each mouse via retro-orbital venipuncture by heparinized microcapillaries. Mice were euthanized and organs removed immediately. The organs were divided into two and either frozen immediately in liquid nitrogen or fixed in 10% formalin and embedded in paraffin for histology. Whenever indicated, 6-week old mice were exposed to hypoxia (8% oxygen for 10 h) followed by 3 h of reoxygenation (21% oxygen) (H/R stress) to mimic an acute VOC, as previously described.

show abstract

“…Echocardiography and global mRNA and miRNA profiling were performed to obtain an overview of global trends and gene regulatory pathways, and to predict optimal preventive therapies. Studies of mitochondrial function and redox in isolated mitochondria and cardiac myocytes (42)(43)(44)(45)(46) were performed to determine the presence of mitochondrial dysfunction (14,32,47) and oxidative stress (19,20), which are implicated in disease pathogenesis.…”

Section: Resultsmentioning

confidence: 99%

“…HCM predisposes to the development of angina, heart failure, and arrhythmias, and is the most common cause of sudden cardiac death in young individuals (1,(3)(4)(5)(6). Biophysical studies have revealed diverse mutation-induced alterations in sarcomeric protein function, which lead to abnormalities in Ca 2+ handling (7)(8)(9)(10)(11)(12), energy metabolism (13)(14)(15)(16)(17)(18) and/or oxidative stress (19)(20)(21). This has prompted the testing of L-type Ca 2+ channel blockers (e.g., diltiazem) (22,23), angiotensin II receptor antagonists (e.g., losartan) (24), antioxidants (e.g., N-acetylcysteine) (21,25,26), and metabolic modulators (perhexiline) (27) with success in preventing hypertrophy, fibrosis, and adverse cardiac remodeling in animal models.…”

Section: Introductionmentioning

confidence: 99%

Allele-specific differences in transcriptome, miRNome, and mitochondrial function in two hypertrophic cardiomyopathy mouse models

Vakrou

Fukunaga²,

Foster

et al. 2018

JCI Insight

View full text Add to dashboard Cite

Enhanced oxidative stress in hypertrophic cardiomyopathy

Cited by 46 publications

References 17 publications

Impaired cardiac mitochondrial oxidative phosphorylation and enhanced mitochondrial oxidative stress in feline hypertrophic cardiomyopathy

Impaired cardiac mitochondrial oxidative phosphorylation and enhanced mitochondrial oxidative stress in feline hypertrophic cardiomyopathy

Dietary -3 fatty acids protect against vasculopathy in a transgenic mouse model of sickle cell disease

Allele-specific differences in transcriptome, miRNome, and mitochondrial function in two hypertrophic cardiomyopathy mouse models

Contact Info

Product

Resources

About