Opposite effects of catalase and MnSOD ectopic expression on stress induced defects and mortality in the desmin deficient cardiomyopathy model

Rapti, Kleopatra; Diokmetzidou, Antigoni; Kloukina, Ismini; Milner, Derek J.; Varela, Aimilia; Davos, Constantinos H.; Capetanaki, Yassemi

doi:10.1016/j.freeradbiomed.2017.06.010

Cited by 23 publications

(34 citation statements)

References 77 publications

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“…1a). We did not notice a substantial rise in mortality during the swimming experiments in contrast to a previous study reporting mortality rates of 50% in desmin deficient mice subjected to the same swimming protocol [28].…”

Section: Resultscontrasting

confidence: 99%

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AAV-mediated cardiac gene transfer of wild-type desmin in mouse models for recessive desminopathies

et al. 2020

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Mutations in the human desmin gene cause autosomal-dominant and recessive cardiomyopathies and myopathies with marked phenotypic variability. Here, we investigated the effects of adeno-associated virus (AAV)-mediated cardiac wildtype desmin expression in homozygous desmin knockout (DKO) and homozygous R349P desmin knockin (DKI) mice. These mice serve as disease models for two subforms of autosomal-recessive desminopathies, the former for the one with a complete lack of desmin protein and the latter for the one with solely mutant desmin protein expression in conjunction with protein aggregation pathology in striated muscle. Two-month-old mice were injected with either a single dose of 5 × 10 12 AAV9-hTNT2-mDes (AAV-Des) vector genomes or NaCl as control. One week after injection, mice were subjected to a forced swimming exercise protocol for 4 weeks. Cardiac function was monitored over a period of 15 month after injection and before the mice were sacrificed for biochemical and morphological analysis. AAV-mediated cardiac expression of wildtype desmin in both the homozygous DKO and DKI backgrounds reached levels seen in wild-type mice. Notably, AAV-Des treated DKO mice showed a regular subcellular distribution of desmin as well as a normalization of functional and morphological cardiac parameters. Treated DKI mice, however, showed an aberrant subcellular localization of desmin, unchanged functional cardiac parameters, and a trend toward an increased cardiac fibrosis. In conclusion, the effect of a high-dose AAV9-based desmin gene therapy is highly beneficial for the heart in DKO animals, but not in DKI mice.

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Section: Resultscontrasting

confidence: 99%

“…A previous study reported that strenuous physical exercise led to a mortality rate of up to 50% in DKO mice [28]. This, however, could not be reproduced in the present study, which employed the same swimming protocol.…”

Section: Aav9-mediated Expression Of Wt Desmin In Dko Mice: a Cure Focontrasting

confidence: 60%

AAV-mediated cardiac gene transfer of wild-type desmin in mouse models for recessive desminopathies

et al. 2020

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“…cardiomyopathy [36,37]. These included ventricular intramyocardial lipid accumulation or ventricular steatosis (Fig 2C), myofibrillar derangement, thinning, and destruction, and mitochondrial hypertrophy (Fig 2C and 2D).…”

Section: Plos Onementioning

confidence: 99%

Electronic cigarettes cause alteration in cardiac structure and function in diet-induced obese mice

et al. 2020

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In spite of the widespread use of electronic cigarettes, also known as e-cigarettes, and the proposed adverse cardiac effects of nicotine, the detrimental effects of e-cigarettes on the heart are not well known. This study examines the detrimental effects of e-cigarettes with nicotine at doses that yield circulating nicotine and cotinine in the ranges similar to the levels found in habitual smokers, and a high fat diet (HFD) on cardiac structure and function in a commonly used model of diet-induced obesity (DIO). C57BL/6J mice on an HFD were exposed to e-cigarette in the presence (2.4% nicotine) or absence (0% nicotine) of nicotine and saline aerosol for 12 weeks. Echocardiographic data demonstrated a decrease in left ventricular (LV) fractional shortening, LV ejection fraction, and velocity of circumferential fiber shortening (VCF) in mice treated with e-cigarette (2.4% nicotine) compared to e-cigarette (0% nicotine) or saline exposed mice. Cardiomyocytes (CMs) of mice treated with ecigarette (2.4% nicotine) exhibited LV abnormalities, including lipid accumulation (ventricular steatosis), myofibrillar derangement and destruction, and mitochondrial hypertrophy, as revealed by transmission electron microscopy. The detrimental effects of e-cigarettes (2.4% nicotine) on cardiac structure and function was accompanied by increased oxidative stress, plasma free fatty acid levels, CM apoptosis, and inactivation of AMP-activated protein kinase and activation of its downstream target, acetyl-CoA-carboxylase. Our results indicate profound adverse effects of e-cigarettes (2.4% nicotine) on the heart in obese mice and raise questions about the safety of the nicotine e-cigarettes use.

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“…Overexpression of the mitochondrial protein Bcl-2, in both the Des −/− and R120GCryAB DRM mouse models, significantly ameliorates the pathology (Weisleder et al 2004b;Maloyan et al 2010). Moreover, moderate MnSOD and/or catalase overexpression in Des −/− hearts resulted in a decreased intracellular reactive oxygen species (ROS), ameliorating mitochondrial and other ultrastructural defects (Rapti et al 2017). The best protection so far has been achieved by αΒcrystallin overexpression in Des −/− heart, where structural and functional defects are rescued to almost wild type levels (Diokmetzidou et al 2016a) (Fig.…”

Section: Loss Of Proper Mitochondrial Function As An Early Prominent mentioning

confidence: 99%

Intermediate filaments in cardiomyopathy

et al. 2018

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Intermediate filament (IF) proteins are critical regulators in health and disease. The discovery of hundreds of mutations in IF genes and posttranslational modifications has been linked to a plethora of human diseases, including, among others, cardiomyopathies, muscular dystrophies, progeria, blistering diseases of the epidermis, and neurodegenerative diseases. The major IF proteins that have been linked to cardiomyopathies and heart failure are the muscle-specific cytoskeletal IF protein desmin and the nuclear IF protein lamin, as a subgroup of the known desminopathies and laminopathies, respectively. The studies so far, both with healthy and diseased heart, have demonstrated the importance of these IF protein networks in intracellular and intercellular integration of structure and function, mechanotransduction and gene activation, cardiomyocyte differentiation and survival, mitochondrial homeostasis, and regulation of metabolism. The high coordination of all these processes is obviously of great importance for the maintenance of proper, life-lasting, and continuous contraction of this highly organized cardiac striated muscle and consequently a healthy heart. In this review, we will cover most known information on the role of IFs in the above processes and how their deficiency or disruption leads to cardiomyopathy and heart failure.

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Opposite effects of catalase and MnSOD ectopic expression on stress induced defects and mortality in the desmin deficient cardiomyopathy model

Cited by 23 publications

References 77 publications

AAV-mediated cardiac gene transfer of wild-type desmin in mouse models for recessive desminopathies

AAV-mediated cardiac gene transfer of wild-type desmin in mouse models for recessive desminopathies

Electronic cigarettes cause alteration in cardiac structure and function in diet-induced obese mice

Intermediate filaments in cardiomyopathy

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