scholarly journals Cellular Physiology of Rat Cardiac Myocytes in Cardiac Fibrosis: In Vitro Simulation Using the Cardiac Myocyte/Cardiac Non-Myocyte Co-Culture System

2008 ◽  
Vol 31 (4) ◽  
pp. 693-706 ◽  
Author(s):  
Keiichi Ikeda ◽  
Katsuyoshi Tojo ◽  
Takashi Udagawa ◽  
Chikara Otsubo ◽  
Masahiro Ishikawa ◽  
...  
Keyword(s):  
Cardiac Myocytes ◽  
Culture System ◽  
Cardiac Fibrosis ◽  
Cardiac Myocyte ◽  
Cellular Physiology ◽  
In Vitro Simulation ◽  
Rat Cardiac Myocytes

scholarly journals Involvement of Cardiotrophin-1 in Cardiac Myocyte-Nonmyocyte Interactions During Hypertrophy of Rat Cardiac Myocytes In Vitro

Circulation ◽  
1999 ◽  
Vol 100 (10) ◽  
pp. 1116-1124 ◽  
Author(s):  
Koichiro Kuwahara ◽  
Yoshihiko Saito ◽  
Masaki Harada ◽  
Masahiro Ishikawa ◽  
Emiko Ogawa ◽  
...  
Keyword(s):  
Cardiac Myocytes ◽  
Cardiac Myocyte ◽  
Rat Cardiac Myocytes

Novel role for cardiac myocyte-derived β-2 microglobulin in mediating cardiac fibrosis

2018 ◽  
Vol 132 (19) ◽  
pp. 2117-2120
Author(s):  
Michael J. Boyer ◽  
Satoru Eguchi
Keyword(s):  
Cardiac Fibrosis ◽  
Cardiac Myocyte ◽  
Cardiac Fibroblasts ◽  
Significant Risk ◽  
Growth Factor Receptor ◽  
Pressure Overload ◽  
Significant Risk Factor ◽  
Cardiac Complications

Hypertension is a significant risk factor for the development of cardiovascular ailments, including ischemic heart disease and diastolic dysfunction. In a recent issue of Clinical Science, Li et al. [Clin. Sci. (2018) 132, 1855–1874] report that β-2 microglobulin (β2M) is a novel secreted soluble factor released by cardiac myocytes during pressure overload that promotes profibrotic gene expression in cardiac fibroblasts both in vitro and in vivo. Their study further identifies elevated β2M levels as a possible biomarker for hypertensive patients with cardiac complications. The authors propose a mechanism that mechanically stretched cardiomyocytes release soluble β2M which, through paracrine communication with cardiac fibroblasts, transactivates epidermal growth factor receptor (EGFR) to initiate acute signal transduction and up-regulate profibrotic genes, thereby promoting fibrosis. Here, we will discuss the background, significance of the study, alternative mechanisms, and future directions.

scholarly journals PDE1C deficiency antagonizes pathological cardiac remodeling and dysfunction

2016 ◽  
Vol 113 (45) ◽  
pp. E7116-E7125 ◽  
Author(s):  
Walter E. Knight ◽  
Si Chen ◽  
Yishuai Zhang ◽  
Masayoshi Oikawa ◽  
Meiping Wu ◽  
...  
Keyword(s):  
Cardiac Myocytes ◽  
Cardiac Remodeling ◽  
Cardiac Fibrosis ◽  
Cardiac Myocyte ◽  
Contractile Function ◽  
Causative Role ◽  
Dependent Manner ◽  
Underlying Mechanisms ◽  
Cardiac Myocyte Hypertrophy

Cyclic nucleotide phosphodiesterase 1C (PDE1C) represents a major phosphodiesterase activity in human myocardium, but its function in the heart remains unknown. Using genetic and pharmacological approaches, we studied the expression, regulation, function, and underlying mechanisms of PDE1C in the pathogenesis of cardiac remodeling and dysfunction. PDE1C expression is up-regulated in mouse and human failing hearts and is highly expressed in cardiac myocytes but not in fibroblasts. In adult mouse cardiac myocytes, PDE1C deficiency or inhibition attenuated myocyte death and apoptosis, which was largely dependent on cyclic AMP/PKA and PI3K/AKT signaling. PDE1C deficiency also attenuated cardiac myocyte hypertrophy in a PKA-dependent manner. Conditioned medium taken from PDE1C-deficient cardiac myocytes attenuated TGF-β–stimulated cardiac fibroblast activation through a mechanism involving the crosstalk between cardiac myocytes and fibroblasts. In vivo, cardiac remodeling and dysfunction induced by transverse aortic constriction, including myocardial hypertrophy, apoptosis, cardiac fibrosis, and loss of contractile function, were significantly attenuated in PDE1C-knockout mice relative to wild-type mice. These results indicate that PDE1C activation plays a causative role in pathological cardiac remodeling and dysfunction. Given the continued development of highly specific PDE1 inhibitors and the high expression level of PDE1C in the human heart, our findings could have considerable therapeutic significance.

Confocal and Electron Microscopy of cultured cardiac myocytes

1993 ◽  
Vol 51 ◽  
pp. 364-365
Author(s):  
D.G. Simpson ◽  
R.L. Price ◽  
M. Terracio ◽  
L. Terracio ◽  
T.K. Borg
Keyword(s):  
Cardiac Myocytes ◽  
Heart Development ◽  
Cardiac Myocyte ◽  
Striated Muscle ◽  
Intercellular Junctions ◽  
Membrane Receptors ◽  
Cell Junctions ◽  
The Many

Early in heart development cardiac myocytes are spherical in shape, intercellular junctions are distributed at irregular intervals around the periphery of the cell, and myofibrillar organization is essentially random. As myocytes mature, they undergo extensive morphogenesis during which the phenotype changes to a tubular rodlike shape, cell junctions congregate at the distal ends of cells to form intercalated disks, and myofibrils become organized in parallel arrays typical of striated muscle. Although not fully understood, it is known that these changes are a result of interactive processes between intracellular components of the cytoskeleton, integrin membrane receptors, and the extracellular matrix (ECM).In vivo studies on the process of cardiac myocyte maturation and myofibrillogenesis are difficult because of the complex biochemical environment of the intact animal and the many extra- and intracellular interactions which are required for proper development and myofibrillogenesis. Unfortunately, in previously available in vitro modelling systems, isolated myocytes spread out over the culture substratum, assume a stellate nonpolar shape, and myofibril organization remains essentially random.

Abstract 127: Phosphorylation of Serum Responsive Factor by p90 Ribosomal S6 Kinase 3 Promotes Concentric Growth of Cardiac Myocytes

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Jinliang Li ◽  
Eliana C Martinez Valencia ◽  
Catherine L Passariello ◽  
Hrishikesh Thakur ◽  
Michael Kapiloff
Keyword(s):  
Cardiac Myocytes ◽  
Cardiac Myocyte ◽  
Pressure Overload ◽  
Post Translational Modification ◽  
S6 Kinase ◽  
Knock Out ◽  
Gene Therapy Vector ◽  
P90 Ribosomal S6 Kinase ◽  
Ribosomal S6 Kinase

p90 Ribosomal S6 Kinase 3 (RSK3) is required for the induction of concentric hypertrophy in hearts subjected to pressure overload and catecholamine infusion, as well as in a model for Noonan Syndrome-associated hypertrophic cardiomyopathy. Serving important roles in both cardiac development and adult function, the transcription factor Serum Responsive Factor (SRF) regulates genes expression involved in myocyte growth and sarcomeric assembly. It has been reported that SRF can be phosphorylated by RSK protein kinases on residue Ser-103, but the function of that post-translational modification has remained uncertain. We now show that SRF is a substrate for RSK3 associated with muscle A-Kinase-Anchoring-Protein (mAKAP) scaffold in cardiac myocytes, contributing to the regulation of concentric myocyte growth. By co-immunoprecipitation assay, SRF and RSK3 were both associated with the mAKAP scaffold in heart extracts, such that a ternary complex could be detected when recombinant proteins were expressed in cells. Silencing RSK3 or mAKAP expression by siRNA transfection reduced phenylephrine-induced SRF(S103) phosphorylation in neonatal cardiac myocytes. Similar results were acquired following expression of a peptide comprising the mAKAP RSK3-binding domain (RBD) that competed the binding of the kinase to the scaffold. Overexpression of either a SRF S103A phosphoablative mutant or the RBD peptide diminished the increase in width of adult cardiac myocytes stimulated by phenylephrine. In contrast, overexpression of RSK3 or a SRF S103D phosphomimetic mutant promoted adult cardiac myocyte concentric hypertorphy in vitro. While baseline SRF S103 phosphorylation in the heart was inhibited by mAKAP or RSK3 gene knock-out in mice, acute transverse aortic constriction significantly increased SRF S103 phosphorylation in the heart. Based upon these results, we porpose that RSK3 phosphorylation of SRF at mAKAP signalosomes is an important regulator of concentric cardiac myocyte growth. These results are consistent with additional findings that an adeno-associated virus gene therapy vector that expresses RBD in the cardiac mycoyte attenuates pathological hypertrophy and prevents heart failure in response to pressure overload.

Cytosolic pH measurements in single cardiac myocytes using carboxy-seminaphthorhodafluor-1

1992 ◽  
Vol 263 (1) ◽  
pp. H276-H284 ◽  
Author(s):  
P. S. Blank ◽  
H. S. Silverman ◽  
O. Y. Chung ◽  
B. A. Hogue ◽  
M. D. Stern ◽  
...  
Keyword(s):  
Cardiac Myocytes ◽  
Spectral Feature ◽  
Ph Measurements ◽  
Dual Emission ◽  
Cytosolic Ph ◽  
Ph Gradients ◽  
In Situ Calibration ◽  
Rat Cardiac Myocytes

This study examines the use of carboxy-seminaphthorhodafluor-1 (C-SNARF-1) as an indicator of cytosolic pH in isolated rat cardiac myocytes. The emission spectrum of C-SNARF-1 when excited at 530 nm contains two well-separated peaks at approximately 590 and 640 nm, corresponding to the acidic and basic forms of the indicator. This spectral feature allows the indicator to be used in the single excitation, dual emission ratio mode. When C-SNARF-1 is loaded into rat cardiac myocytes as the membrane permeant ester derivative, C-SNARF-1/AM, the indicator localizes within the cytosol with virtually no partitioning into the mitochondria. C-SNARF-1 does not load into isolated mitochondria in suspension. There was no evidence for the presence of non-deesterified C-SNARF-1 within the cells. C-SNARF-1 can be calibrated in situ using a technique that abolishes all transsarcolemmal pH gradients. A 0.7-unit shift in the apparent pK (pKapp = pK-log10) between the in vitro calibration and the in situ calibration is consistent with a change in beta (I640 to pH 9/I640 at pH 5) in the cytosolic environment (beta in situ/beta in vitro = 0.21) and not a change in the true pK of the indicator. The contribution of cellular autofluorescence to the total signal can be made negligible. There is no effect of C-SNARF-1 on the contractile properties of rat cardiac myocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Over Expression of Plk1 Does Not Induce Cell Division in Rat Cardiac Myocytes In Vitro

PLoS ONE ◽  
2009 ◽  
Vol 4 (8) ◽  
pp. e6752 ◽  
Author(s):  
Carmen H. Coxon ◽  
Katrina A. Bicknell ◽  
Fleur L. Moseley ◽  
Gavin Brooks
Keyword(s):  
Cell Division ◽  
Cardiac Myocytes ◽  
Over Expression ◽  
Induce Cell Division ◽  
Rat Cardiac Myocytes

Cardiac myocyte guanosine transport and metabolism

1987 ◽  
Vol 253 (5) ◽  
pp. C645-C651 ◽  
Author(s):  
T. P. Geisbuhler ◽  
D. A. Johnson ◽  
M. J. Rovetto
Keyword(s):  
Cardiac Myocytes ◽  
Rate Constant ◽  
Cardiac Myocyte ◽  
Maximum Velocity ◽  
Guanine Nucleotides ◽  
Inhibition Constant ◽  
Adult Rat ◽  
Adenosine Transport ◽  
Common Carrier ◽  
Rat Cardiac Myocytes

Guanosine transport and metabolism were examined in adult rat cardiac myocytes. Myocytes transported guanosine via saturable [Km = 18 microM, maximum velocity (Vmax) = 3.61 pmol.mg-1.s-1] and nonsaturable (rate constant = 1.47 X 10(-2] processes. The saturable process was inhibited by nitrobenzyl-thioinosine, inosine [inhibition constant (Ki) = 180 microM], and adenosine (Ki = 112 microM). Extracellular guanosine taken up by myocytes was slowly phosphorylated to guanine nucleotides. The majority of guanosine (98%) existed as free intracellular guanosine after 60 s. Countertransport of nucleosides could not be demonstrated in these cells at physiological concentrations in the presence of up to a 10-fold gradient of nucleoside. These studies indicate that adult rat cardiac myocytes can be used to assess myocardial guanosine transport separate from its metabolism. Comparable inhibition of guanosine and adenosine transport by each other and by inosine support the hypothesis that guanosine and adenosine are transported by a common carrier.

Gene silencing in adult rat cardiac myocytes in vitro by adenovirus-mediated RNA interference

2006 ◽  
Vol 27 (5-7) ◽  
pp. 413-421 ◽  
Author(s):  
Andreas Rinne ◽  
Christoph Littwitz ◽  
Marie-Cécile Kienitz ◽  
Andreas Gmerek ◽  
Leif I. Bösche ◽  
...  
Keyword(s):  
Rna Interference ◽  
Gene Silencing ◽  
Cardiac Myocytes ◽  
Adult Rat ◽  
Rat Cardiac Myocytes
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