Alteration of endogenous antioxidant enzymes in naturally occurring hypertrophic cardiomyopathy

Lin, Chih‐Sheng; Liu, Chang Yeu; Sun, Yu; Chang, Ling; Chiu, Yu‐Chiao; Huang, San Yuan; Lin, Jyh Hung; Yang, Ping; Chu, Redman; Huang, Mengyi; Mao, Simon J.T.

doi:10.1080/15216549700205081

Cited by 13 publications

(10 citation statements)

References 3 publications

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“…Accordingly, in symptomatic HCM patients, lower catalase activity is observed, while the levels of other antioxidant enzymes, including mitochondrial superoxide dismutase (SOD) and glutathione peroxidase (GPX), are unaltered [87]. Similar findings were reported in a pig model of naturally occurring HCM [88]. Notably, elevated oxidative stress is an established driver of left ventricular hypertrophy and fibrosis in HCM models [84][85][86][89][90][91], which suggests that this event precedes the progression of the disease from the asymptomatic to the symptomatic form.…”

Section: Hypertrophic Cardiomyopathysupporting

confidence: 58%

Metabolic Alterations in Inherited Cardiomyopathies

Sacchetto

Sequeira

Bertero

et al. 2019

JCM

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The normal function of the heart relies on a series of complex metabolic processes orchestrating the proper generation and use of energy. In this context, mitochondria serve a crucial role as a platform for energy transduction by supplying ATP to the varying demand of cardiomyocytes, involving an intricate network of pathways regulating the metabolic flux of substrates. The failure of these processes results in structural and functional deficiencies of the cardiac muscle, including inherited cardiomyopathies. These genetic diseases are characterized by cardiac structural and functional anomalies in the absence of abnormal conditions that can explain the observed myocardial abnormality, and are frequently associated with heart failure. Since their original description, major advances have been achieved in the genetic and phenotype knowledge, highlighting the involvement of metabolic abnormalities in their pathogenesis. This review provides a brief overview of the role of mitochondria in the energy metabolism in the heart and focuses on metabolic abnormalities, mitochondrial dysfunction, and storage diseases associated with inherited cardiomyopathies.

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Section: Hypertrophic Cardiomyopathysupporting

confidence: 58%

Metabolic Alterations in Inherited Cardiomyopathies

Sacchetto

Sequeira

Bertero

et al. 2019

JCM

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“…19 Other redoxregulating proteins, such as thioredoxin (TXN), GPX1, and Cu-Zn superoxide dismutase (SOD1) also have been implicated in regulating cardiac hypertrophy and failure. 18,20,21 We detected no significant changes in the expression levels of GPX1 and HOMX1 in the ␤-MyHC-Q403 rabbits. We could not determine expression levels of TXN and SOD in the heart because of lack of reliable assays in rabbits.…”

Section: Circulation Research August 5 2005mentioning

confidence: 77%

“…Decreased expression level of CAT mRNA has been observed in a porcine model with naturally occurring HCM. 18 Catalase, which reacts very efficiently with H 2 O 2 to form water and molecular oxygen, in conjunction with GPX1 are the primary responsible enzymes for the removal of H 2 O 2 . Although it is plausible that reduced expression level of CAT could provide for a mechanism for the excess levels of H 2 O 2 in the hypertrophic conditions, we did not detect significant reduc- …”

Section: Discussionmentioning

confidence: 99%

Prevention of Cardiac Hypertrophy by Atorvastatin in a Transgenic Rabbit Model of Human Hypertrophic Cardiomyopathy

Senthil

Chen

Tsybouleva

et al. 2005

Circulation Research

135

116

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Abstract-Cardiac hypertrophy, a major determinant of morbidity and mortality in hypertrophic cardiomyopathy (HCM), is considered a secondary phenotype and potentially preventable. To test this hypothesis, we screened 30 5-to 6-month-old ␤-myosin heavy chain Q403 transgenic rabbits by echocardiography and selected 26 without cardiac hypertrophy. We randomized the transgenic rabbits to treatment with atorvastatin (2.5 mg/Kg/d), known to block hypertrophic signaling or a placebo. We included 15 nontransgenic rabbits as controls. Cardiac phenotype was analyzed serially before, 6 and 12 months after randomization. Serum total cholesterol levels were reduced by 49% with atorvastatin administration. Left-ventricular mass, wall thickness; myocyte size, myocardial levels of molecular markers of hypertrophy, lipid peroxides, and oxidized mitochondrial DNA; and the number of terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL)-positive myocytes were increased significantly in the placebo but not in the atorvastatin group. Myocardium catalase mRNA levels were decreased by 5-fold in the placebo but were normal in the atorvastatin group. Catalase protein level and activity were not significantly changed. Levels of membrane-bound Ras and phospho-p44/42 mitogen-activated-protein kinase (MAPK) were increased in the placebo group (Ϸ2.5 fold) but were reduced in the atorvastatin group. Levels of GTP-and membrane-bound RhoA and Rac1, phospho-p38, and phospho-c-Jun NH2-terminal kinases were unchanged. Thus, atorvastatin prevented development of cardiac hypertrophy; determined at organ, cellular, and molecular levels, partly through reducing active Ras and p44/42 MAPK. The results indicate potential beneficial effects of atorvastatin in prevention of cardiac hypertrophy, a major determinant of morbidity in all forms of cardiovascular diseases, and beckon clinical studies in humans with HCM.

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“…Moreover, in general, oxidative stress is determined by an imbalance between ROS and antioxidant-defense capacity, and it has been reported that the activity of catalase, an antioxidant, is decreased in hearts from a porcine model of spontaneously occurring HCM (28), which suggests that lower antioxidant capacity may also contribute to the enhanced oxidative stress in HCM hearts.…”

Section: Other Possible Sources Of Enhanced Oxidative Stress In the Hmentioning

confidence: 99%

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

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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

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Alteration of endogenous antioxidant enzymes in naturally occurring hypertrophic cardiomyopathy

Cited by 13 publications

References 3 publications

Metabolic Alterations in Inherited Cardiomyopathies

Metabolic Alterations in Inherited Cardiomyopathies

Prevention of Cardiac Hypertrophy by Atorvastatin in a Transgenic Rabbit Model of Human Hypertrophic Cardiomyopathy

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

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