Morphological manifestations of heart remodeling in anthracycline-induced dilated cardiomyopathy

Лушникова, Е. Л.; Клинникова, М. Г.; Молодых, О. П.; Nepomnyashchikh, L. M.

doi:10.1007/s10517-005-0138-0

Cited by 15 publications

(11 citation statements)

References 9 publications

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“…The myoblastic cell line H9c2 (Kimes and Brandt 1976) is a well-characterized in vitro system used to study Dox-induced biochemical changes and the protective effect of a wide number of compounds (Chua et al 2006;L'Ecuyer et al 2006;Spallarossa et al 2004;Wattanapitayakul et al 2005). For example, a recent study demonstrated that Dox treatment leads to hypertrophy of H9c2 cells (Merten et al 2006), similar to what has been observed in adult cardiomyocytes during the development of the Dox-induced cardiomyopathy (Lushnikova et al 2004). Despite some work conducted on the biochemical alterations of H9c2 cells induced by Dox, the evaluation and characterization of morphological modifications has not been extensively studied.…”

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confidence: 86%

Morphological alterations induced by doxorubicin on H9c2 myoblasts: nuclear, mitochondrial, and cytoskeletal targets

et al. 2008

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Doxorubicin (Dox) is a very potent antineoplastic agent used against several types of cancer, despite a cumulative cardiomyopathy that reduces the therapeutic index for treatment. H9c2 myoblast cells have been used as an in vitro model to study biochemical alterations induced by Dox treatment on cardiomyocyte cells. Despite the extensive work already published, few data are available regarding morphological alterations of H9c2 cells during Dox treatment. The purpose of the present work was to evaluate Doxinduced morphological alterations in H9c2 myoblasts, focusing especially on the nuclei, mitochondria, and structural fibrous proteins. Treatment of H9c2 cell with low concentrations of Dox causes alterations in fibrous structural proteins including the nuclear lamina and sarcomeric cardiac myosin, as well as mitochondrial depolarization and fragmentation, membrane blebbing with cell shape changes, and phosphatidylserine externalization. For higher Dox concentrations, more profound alterations are evident, including nuclear swelling with disruption of nuclear membrane structure, mitochondrial swelling, and extensive cytoplasm vacuolization. The results obtained indicate that Dox causes morphological alterations in mitochondrial, nuclear, and fibrous protein structures in H9c2 cells, which are dependent on the drug concentration. Data obtained with the present study allow for a better characterization of the effects of Dox on H9c2 myoblasts, used as a model to study Dox-induced cardiotoxicity. The results obtained also provide new and previously unknown targets that can contribute to understand the mechanisms involved in the cardiotoxicity of Dox.

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confidence: 86%

Morphological alterations induced by doxorubicin on H9c2 myoblasts: nuclear, mitochondrial, and cytoskeletal targets

et al. 2008

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“…Pathological studies on experimental animal models and human endomyocardial biopsies have shown that anthracycline-induced cardiomyopathy is characterized by histological alterations consisting in multiple areas of interstitial fibrosis associated with the presence of cardiomyocytes with vacuolar degeneration or compensatory hypertrophy. Necrotic cardiomyocytes with cellular infiltration, stromal edema with myocardial fibers dissociation, and the presence of polymorphonuclear cells can also be observed [6–8]. …”

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confidence: 99%

Carvedilol-Afforded Protection against Daunorubicin-Induced Cardiomyopathic Rats In Vivo: Effects on Cardiac Fibrosis and Hypertrophy

et al. 2011

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Anthracyclines, most powerful anticancer agents, suffer from their cardiotoxic effects, which may be due to the induction of oxidative stress. Carvedilol, a third-generation, nonselective β-adrenoreceptor antagonist, possesses both reactive oxygen species (ROS) scavenging and ROS suppressive effects. It showed protective effects against daunorubicin- (DNR-) induced cardiac toxicity by reducing oxidative stress and apoptosis. This study therefore was designed to examine the effects of carvedilol on DNR-induced cardiomyopathic rats, focused on the changes of left ventricular function, cardiac fibrosis, and hypertrophy. Carvedilol increased survival rate, prevented systolic and diastolic dysfunction, and attenuated myocardial fibrosis and hypertrophy. DNR alone treated rats showed upregulated myocardial expression of ANP, PKC-α, OPN, and TGF-β1 and downregulation of GATA-4 in comparison with control, and treatment with carvedilol significantly reversed these changes. The results of the present study add the available evidences on the cardioprotection by carvedilol when associated with anthracyclines and explain the mechanisms underlying the benefits of their coadministration.

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“…Experimental study of structural mechanisms of dilated cardiomyopathy (at the tissue, cellular, and intracellular levels) showed that heart remodeling by the dilatation variant is caused by the development of regeneratory and plastic insufficiency of cardiomyocytes (CMC), followed by apoptosis and appreciable loss of these cells [1,4]. Diffuse CMC apoptosis can cause a 10-30% decrease in their total count, which serves as the triggering mechanism for dilatation remodeling [2,6,7,12].…”

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confidence: 99%

Ultrastructural Criteria of Cardiomyocyte Regeneratory and Plastic Insufficiency in Anthracycline Cardiomyopathy

et al. 2005

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We analyzed the dynamics of ultrastructural changes in cardiomyocytes in experimental chronic anthracycline cardiomyopathy. Doxorubicin-induced changes in cardiomyocytes were characterized by a specific combination of ultrastructural changes, which can be regarded as markers of the development of regeneratory and plastic insufficiency. These markers include a triad of changes: deformation of the nuclei with reorganization of the nucleolar system; diffuse and small focal lysis of myofibrils (mainly fine filaments); dilatation of agranular sarcoplasmic reticulum and the intermembrane perinuclear space connected to it. The terminal stages of these disorders are degeneration of some cardiomyocytes, their apoptotic death, and resorption by mononuclear cells (processes representing successive stages in the development of regeneratory and plastic insufficiency of the myocardium).

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Morphological manifestations of heart remodeling in anthracycline-induced dilated cardiomyopathy

Cited by 15 publications

References 9 publications

Morphological alterations induced by doxorubicin on H9c2 myoblasts: nuclear, mitochondrial, and cytoskeletal targets

Morphological alterations induced by doxorubicin on H9c2 myoblasts: nuclear, mitochondrial, and cytoskeletal targets

Carvedilol-Afforded Protection against Daunorubicin-Induced Cardiomyopathic Rats In Vivo: Effects on Cardiac Fibrosis and Hypertrophy

Ultrastructural Criteria of Cardiomyocyte Regeneratory and Plastic Insufficiency in Anthracycline Cardiomyopathy

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