Increased Expression of Cytoskeletal, Linkage, and Extracellular Proteins in Failing Human Myocardium

Heling, Annette; Zimmermann, René; Kostin, Sawa; Maeno, Yoshi; Hein, Stefan; Devaux, Bruno; Bauer, Erwin; Klövekorn, W. P.; Schlepper, M; Schäper, Wolfgang; Schaper, Jutta

doi:10.1161/01.res.86.8.846

Cited by 289 publications

(256 citation statements)

References 49 publications

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“…Previous studies demonstrated that alterations in cytoskeletal proteins can induce cardiomyopathy (Heling et al 2000) and that these alterations also occur in aging cardiomyopathy (Heling et al 2000;Lieber et al 2008). We found that cardiac cytoskeletal proteins in old normal mice were increased, e.g., α-tubulin, β-tubulin, and cleaved desmin, whereas intact desmin was decreased.…”

supporting

confidence: 46%

Calorie restriction can reverse, as well as prevent, aging cardiomyopathy

Yan

Gao

et al. 2013

AGE

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Calorie restriction (CR) is the most widely studied intervention protecting from the adverse effects of aging. Almost all prior studies have examined the effects of CR initiated in young animals. Studies examining the effects of CR on development of aging cardiomyopathy found only partial prevention. The major goal of this study was to determine whether CR initiated after aging cardiomyopathy developed could reverse the cardiomyopathy. Aging cardiomyopathy in 2-year-old mice was characterized by reduced left ventricular (LV) function, cardiac hypertrophy, and increased cardiac apoptosis and fibrosis. When short-term (2 months) CR was initiated after aging cardiomyopathy developed in 20-month-old mice, the decrease in cardiac function, and increases in LV weight, myocardial fibrosis and apoptosis were reversed, such that the aging hearts in these mice were indistinguishable from those of young mice or mice where CR was initiated in young mice. If apoptosis was the mechanism for protecting against aging cardiomyopathy, then total myocyte numbers should have reverted to normal with CR, but did not. However, the alterations in cytoskeletal proteins, which contribute to aging cardiomyopathy, were no longer observed with CR. This is the first study to demonstrate complete prevention of aging cardiomyopathy by CR and, more importantly, that instituting this intervention even later in life can rapidly correct aging cardiomyopathy, which could have important therapeutic implications.

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supporting

confidence: 46%

Calorie restriction can reverse, as well as prevent, aging cardiomyopathy

Yan

Gao

et al. 2013

AGE

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“…This was confirmed by a study from our group showing an increase in tubulin protein and its mRNA in failing hearts from patients with dilated cardiomyopathy. In our work, however, in addition to tubulin other proteins such as desmin and vinculin were found to be augmented while the contractile proteins actin and myosin and the major component of the sarcomeric skeleton titin were significantly reduced (5,14). This indicates that changes in the microtubular system certainly are important, especially for the rate of protein synthesis as shown in the paper under discussion, but that other molecular changes occur as well and may significantly influence the course of hypertrophy and heart failure.…”

contrasting

confidence: 55%

mRNA cargo no longer on time

Hein¹,

Kostin²,

Schaper³

2008

American Journal of Physiology-Heart and Circulatory Physiology

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“…2,3 These functional alterations have a structural basis involving cellular and interstitial changes that manifest as differences in size, shape, and extracellular matrix properties. 4 These morphological alterations have been proposed to occur in response to injury or stress stimulus and may be an adaptive response to overcome depressed cardiac function.…”

mentioning

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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Increased Expression of Cytoskeletal, Linkage, and Extracellular Proteins in Failing Human Myocardium

Cited by 289 publications

References 49 publications

Calorie restriction can reverse, as well as prevent, aging cardiomyopathy

Calorie restriction can reverse, as well as prevent, aging cardiomyopathy

mRNA cargo no longer on time

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

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