Cytoskeletal remodeling of desmin is a more accurate measure of cardiac dysfunction than fibrosis or myocyte hypertrophy

Monreal, Gretel; Nicholson, Lisa; Han, Bing; Joshi, Mandar; Phillips, Alistair; Wold, Loren E.; Bauer, John; Gerhardt, Mark A.

doi:10.1016/j.lfs.2008.09.026

Cited by 39 publications

(38 citation statements)

References 34 publications

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“…Desmin, a structural protein that links myofibirils at Z-disks and maybe involved in force transmission [31], has been proposed as a potential biomarker for heart failure [32,33]. Pawlak et al [33] had previously shown that desmin content is increased in endocardial biopsies from patients with heart failure and this result was confirmed in the present work ( Figure 5C).…”

Section: Proteins That Influence Power Outputsupporting

confidence: 85%

Transmural Heterogeneity of Cellular Level Power Output Is Reduced in Human Heart Failure

Haynes

Nava

Lawson

et al. 2014

The Journal of Heart and Lung Transplantation

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Section: Proteins That Influence Power Outputsupporting

confidence: 85%

Transmural Heterogeneity of Cellular Level Power Output Is Reduced in Human Heart Failure

Haynes

Nava

Lawson

et al. 2014

The Journal of Heart and Lung Transplantation

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“…Disorganization of desmin and mitochondria functional complexes with myofibrils and the sarcoplasmic reticulum have been shown to be present before the onset of cardiac and skeletal muscle failure (3, 6, 24 -28, 36, 38). The relation of desmin breakdown to long-term survival and to the severity of LV dysfunction in human heart failure (13,29,32,33) provides further evidence for a nongenetic cause of desmin degradation in the pathophysiology of LV functional deterioration.…”

Section: Discussionmentioning

confidence: 99%

Cardiomyocyte mitochondrial oxidative stress and cytoskeletal breakdown in the heart with a primary volume overload

Yancey

Guichard

Ahmed

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

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Left ventricular (LV) volume overload (VO) results in cardiomyocyte oxidative stress and mitochondrial dysfunction. Because mitochondria are both a source and target of ROS, we hypothesized that the mitochondrially targeted antioxidant mitoubiquinone (MitoQ) will improve cardiomyocyte damage and LV dysfunction in VO. Isolated cardiomyocytes from Sprague-Dawley rats were exposed to stretch in vitro and VO of aortocaval fistula (ACF) in vivo. ACF rats were treated with and without MitoQ. Isolated cardiomyocytes were analyzed after 3 h of cyclical stretch or 8 wk of ACF with MitoSox red or 5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate to measure ROS and with tetramethylrhodamine to measure mitochondrial membrane potential. Transmission electron microscopy and immunohistochemistry were used for cardiomyocyte structural assessment. In vitro cyclical stretch and 8-wk ACF resulted in increased cardiomyocyte mitochondrial ROS production and decreased mitochondrial membrane potential, which were significantly improved by MitoQ. ACF had extensive loss of desmin and β₂-tubulin that was paralleled by mitochondrial disorganization, loss of cristae, swelling, and clustering identified by mitochondria complex IV staining and transmission electron microscopy. MitoQ improved mitochondrial structural damage and attenuated desmin loss/degradation evidenced by immunohistochemistry and protein expression. However, LV dilatation and fractional shortening were unaffected by MitoQ treatment in 8-wk ACF. In conclusion, although MitoQ did not affect LV dilatation or function in ACF, these experiments suggest a connection of cardiomyocyte mitochondria-derived ROS production with cytoskeletal disruption and mitochondrial damage in the VO of ACF.

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“…9,24 It was proposed that an increase in cytoskeletal membrane-associated proteins accompanied by loss of contractile filaments are the main changes that may be regarded as the morphological causes of heart dysfunction. 25,26 Although the number of genes known to be involved in structural disuption in HF increases every year, a large number of cytoskeleton and effector genes were not discussed yet. Therefore, the objective of this study was to highlight a select group of cytoskeleton genes and effectors using RNA-Seq, comparing patients with ICM and nonischemic DCM to CNT, and to find out their functional relationship.…”

Section: Discussionmentioning

confidence: 99%

RNA-sequencing analysis reveals new alterations in cardiomyocyte cytoskeletal genes in patients with heart failure

Herrer

Roselló‐Lletí

Rivera

et al. 2014

Laboratory Investigation

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Changes in cardiomyocyte cytoskeletal components, a crucial scaffold of cellular structure, have been found in heart failure (HF); however, the altered cytoskeletal network remains to be elucidated. This study investigated a new map of cytoskeleton-linked alterations that further explain the cardiomyocyte morphology and contraction disruption in HF. RNA-Sequencing (RNA-Seq) analysis was performed in 29 human LV tissue samples from ischemic cardiomyopathy (ICM; n ¼ 13) and dilated cardiomyopathy (DCM, n ¼ 10) patients undergoing cardiac transplantation and six healthy donors (control, CNT) and up to 16 ICM, 13 DCM and 7 CNT tissue samples for qRT-PCR. Gene Ontology analysis of RNA-Seq data demonstrated that cytoskeletal processes are altered in HF. We identified 60 differentially expressed cytoskeleton-related genes in ICM and 58 genes in DCM comparing with CNT, hierarchical clustering determined that shared cytoskeletal genes have a similar behavior in both pathologies. We further investigated MYLK4, RHOU, and ANKRD1 cytoskeletal components. qRT-PCR analysis revealed that MYLK4 was downregulated ( À 2.2-fold; Po0.05) and ANKRD1 was upregulated (2.3-fold; Po0.01) in ICM patients vs CNT. RHOU mRNA levels showed a statistical trend to decrease ( À 2.9-fold). In DCM vs CNT, MYLK4 ( À 4.0-fold; Po0.05) and RHOU ( À 3.9-fold; Po0.05) were downregulated and ANKRD1 (2.5-fold; Po0.05) was upregulated. Accordingly, MYLK4 and ANKRD1 protein levels were decreased and increased, respectively, in both diseases. Furthermore, ANKRD1 and RHOU mRNA levels were related with LV function (Po0.05). In summary, we have found a new map of changes in the ICM and DCM cardiomyocyte cytoskeleton. ANKRD1 and RHOU mRNA levels were related with LV function which emphasizes their relevance in HF. These new cytoskeletal changes may be responsible for altered contraction and cell architecture disruption in HF patients. Moreover, these results improve our knowledge on the role of cytoskeleton in functional and structural alterations in HF.

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Cytoskeletal remodeling of desmin is a more accurate measure of cardiac dysfunction than fibrosis or myocyte hypertrophy

Cited by 39 publications

References 34 publications

Transmural Heterogeneity of Cellular Level Power Output Is Reduced in Human Heart Failure

Transmural Heterogeneity of Cellular Level Power Output Is Reduced in Human Heart Failure

Cardiomyocyte mitochondrial oxidative stress and cytoskeletal breakdown in the heart with a primary volume overload

RNA-sequencing analysis reveals new alterations in cardiomyocyte cytoskeletal genes in patients with heart failure

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