The Overall Pattern of Cardiac Contraction Depends on a Spatial Gradient of Myosin Regulatory Light Chain Phosphorylation

Davis, Julien S.; Hassanzadeh, Shakiba; Winitsky, Steve; Lin, Hua; Satorius, Colleen; Vemuri, Ramesh; Aletras, Anthony H.; Wen, Han; Epstein, Neal D.

doi:10.1016/s0092-8674(01)00586-4

Cited by 245 publications

(270 citation statements)

References 27 publications

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“…MLC2 has a major role in regulating cardiac function, and therefore MLC2 phosphorylation status, regulated by MLCKs, is critical to this process. 30 Chan et al identified a new MLCK that is specifically expressed in the heart, MLCK3, or cardiac MLCK. 31 The downregulation of cardiac MLCK decreases the steady-state levels of MLC2 phosphorylated; therefore, it was proposed to be the main myosin kinase acting on cardiac myocytes.…”

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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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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“…During ejection, myofibers shorten across the entire transmural wall of the LV. However, the direction of rotation is governed by the subepicardial fibers owing to their longer arm of movement (50) and their intrinsic contractile properties (51). Shortening of subepicardial fibers results in counterclockwise rotation of the LV apex and clockwise rotation of the LV base.…”

Section: Sequence Of the LV Rotationmentioning

confidence: 99%

Left Ventricular Form and Function Revisited: Applied Translational Science to Cardiovascular Ultrasound Imaging

Sengupta

Krishnamoorthy

Kořínek

et al. 2007

Journal of the American Society of Echocardiography

287

196

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Tissue Doppler imaging (TDI) and TDI-derived strain imaging are robust physiologic tools used for the noninvasive assessment of regional myocardial function. Due to high temporal and spatial resolution, regional function can be assessed for each phase of the cardiac cycle and within the transmural layers of the myocardial wall. Newer techniques that measure myocardial motion by speckle tracking in grayscale images have overcome the angle dependence of TDI strain, allowing for measurement of 2-dimensional strain and cardiac rotation. TDI, TDI strain, and speckle tracking may provide unique information that deciphers the deformation sequence of complexly oriented myofibers in the left ventricular wall. The data are, however, limited. This review examines the structure and function of the left ventricle relative to the potential clinical application of TDI and speckle tracking in assessing the global mechanical sequence of the left ventricle in vivo.The spiral arrangement of muscle fibers in the heart is reminiscent of spiral and vortex patterns in nature, ranging from small organelles and whirlpools to hurricanes and rotational patterns of the galaxies (1-5). Vortex patterns link two fundamental forms of motion that work in close balance: an inner, rapidly descending swirl and an outer, less rapid, ascending rotation (4) ( Fig. 1 A-C). These counterdirectional movements of a vortex produce suction and expulsion forces that have been exploited for designing energy efficient propellers and turbines (6). Likewise, experimental and mathematical modeling of the clockwise and counterclockwise spiral loops of myofibers in the left ventricle (LV) has shown that counterdirectional geometry provides an efficient distribution of regional stresses and strains (7). Conversely, altered ventricular geometry resulting from cardiac remodeling, regional myocardial dysfunction, or asynchronous conduction distort the efficiency of the loading and expulsion dynamics (8,9). In this review, we associate the LV myofiber architecture to the spatiotemporal sequence of regional deformations occurring during normal cardiac contraction and relaxation. We further elucidate experimental observations, which explore the application of tissue Doppler imaging (TDI) and 2-dimensional ultrasound speckle tracking for delineation of the synchronous mechanical shortening and lengthening sequences of the human LV.Address reprint requests to Marek Belohlavek, Division of Cardiovascular Diseases, Mayo Clinic, 13400 East Shea Boulevard Scottsdale, AZ 85259, E-mail address for author named in reprint line: Belohlavek.marek@mayo.edu Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect th...

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“…This finding also suggests the peptide antibodies may not bind to modified isoforms, as phosphorylated forms, or to secreted forms where cleavage of the secreted protein may have taken place. It is known that the phosphorylation status of myosin II is important in intracellular tension and is associated with stress fibers, whereby signaling can occur by means of the ROCK-RhoA-kinase pathway regulating the phosphorylation level of myosin II (Vemuri et al, 1999;Davis et al, 2001;Epstein and Davis, 2003;Kawabata et al, 2004). Interestingly, inhibition of Rho kinases by Y27632 blocks normal heart development and normal left-right asymmetry (Wei et al, 2001(Wei et al, , 2002.…”

Section: Nonmuscle Myosin II Proteins and Heart Loopingmentioning

confidence: 99%

Cellular nonmuscle myosins NMHC‐IIA and NMHC‐IIB and vertebrate heart looping

Lu¹,

Seeholzer²,

Han³

et al. 2008

Developmental Dynamics

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Flectin, a protein previously described to be expressed in a left-dominant manner in the embryonic chick heart during looping, is a member of the nonmuscle myosin II (NMHC-II) protein class. During looping, both NMHC-IIA and NMHC-IIB are expressed in the mouse heart on embryonic day 9.5. The patterns of localization of NMHC-IIB, rather than NMHC-IIA in the mouse looping heart and in neural crest cells, are equivalent to what we reported previously for flectin. Expression of full-length human NMHC-IIA and -IIB in 10 T1/2 cells demonstrated that flectin antibody recognizes both isoforms. Electron microscopy revealed that flectin antibody localizes in short cardiomyocyte cell processes extending from the basal layer of the cardiomyocytes into the cardiac jelly. Flectin antibody also recognizes stress fibrils in the cardiac jelly in the mouse and chick heart; while NMHC-IIB antibody does not. Abnormally looping hearts of the Nodal ⌬ 600 homozygous mouse embryos show decreased NMHC-IIB expression on both the mRNA and protein levels. These results document the characterization of flectin and extend the importance of NMHC-II and the cytoskeletal actomyosin complex to the mammalian heart and cardiac looping. Developmental Dynamics 237:3577-3590, 2008.

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The Overall Pattern of Cardiac Contraction Depends on a Spatial Gradient of Myosin Regulatory Light Chain Phosphorylation

Cited by 245 publications

References 27 publications

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

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

Left Ventricular Form and Function Revisited: Applied Translational Science to Cardiovascular Ultrasound Imaging

Cellular nonmuscle myosins NMHC‐IIA and NMHC‐IIB and vertebrate heart looping

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