Expression of ventricular-type myosin light chain messenger RNA in spontaneously hypertensive rat atria.

Kumar, Chandan; Saidapet, Chandrika; Delaney, Pamela; Mendola, Charmaine E.; Siddiqui, M.A.Q.

doi:10.1161/01.res.62.6.1093

Cited by 23 publications

(17 citation statements)

References 30 publications

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“…The most important determinant of LVH in SHR is the transverse growth of cardiomyocytes, which has been previously reported both in cardiac tissue and in isolated cells [21,22]. Similarly, other groups have demonstrated an increase mRNA expression of the contractile protein MLC-2v [23,24] and the embryonic gene skeletal α-actin [25] in this experimental model. Several cardiomyocyte growth factors, including endothelin, angiotensin II and α-adrenergic stimulation, upregulate the expression of MLC-2v [26][27][28][29] and skeletal α-actin [30][31][32].…”

Section: Discussionsupporting

confidence: 80%

Differential hypertrophic effects of cardiotrophin-1 on adult cardiomyocytes from normotensive and spontaneously hypertensive rats

López

Dı́ez

Fortuño

2006

Journal of Molecular and Cellular Cardiology

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Cardiotrophin-1 (CT-1) produces longitudinal elongation of neonatal cardiomyocytes, but its effects in adult cardiomyocytes are not known. Recent observations indicate that CT-1 may be involved in pressure overload left ventricular hypertrophy (LVH). We investigated whether the hypertrophic effects of CT-1 are different in cardiomyocytes isolated from adult normotensive and spontaneously hypertensive rats (SHR). Hypertrophy was evaluated by planimetry and confocal microscopy, contractile proteins were quantified by Western blotting and real-time RT-PCR, and intracellular pathways were analyzed with specific chemical inhibitors. CT-1 increased c-fos and ANP expression (p < 0.01) and cell area (p < 0.01) in cardiomyocytes from both rat strains. In Wistar cells, CT-1 augmented cell length (p < 0.01) but did not modify either the transverse diameter or cell depth. In SHR cells, CT-1 increased cell length (p < 0.05), cell width (p < 0.01) and cell depth, augmented the expression of myosin light chain-2v (MLC-2v) and skeletal α-actin (p < 0.01) and enhanced MLC-2v phosphorylation (p < 0.01). The blockade of gp130 or LIFR abolished CT-1-induced growth in the two cell types. All distinct effects observed in cardiomyocytes from SHR were mediated by STAT3. Baseline angiotensinogen expression was higher in SHR cells, and CT-1 induced a 1.7-fold and 3.2-fold increase of angiotensinogen mRNA in cardiomyocytes from Wistar rats and SHR respectively. In addition, AT1 blockade inhibited the specific effects of CT-1 in SHR cells. Finally, ex vivo determinations revealed that adult SHR exhibited enhanced myocardial CT-1 (mRNA and protein, p < 0.01), increased cell width (p < 0.01) and concentric LVH compared with pre-hypertensive SHR. These findings reveal a specific cell-broadening effect of CT-1 in cardiomyocytes from adult SHR and suggest that the hypertensive phenotype of these cells may influence the hypertrophic effects of CT-1, probably by means of an exaggerated induction of angiotensinogen expression. We suggest that CT-1 might facilitate LVH in genetic hypertension through a cross-talk with the renin-angiotensin system.

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Section: Discussionsupporting

confidence: 80%

Differential hypertrophic effects of cardiotrophin-1 on adult cardiomyocytes from normotensive and spontaneously hypertensive rats

López

Dı́ez

Fortuño

2006

Journal of Molecular and Cellular Cardiology

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“…Consistent with this notion, TG1 ventricles had significant down-regulation of myosin light chain 2 ventricular isoform (MLC2V) (63 Ϯ 19 versus 100 Ϯ 17, P ϭ 0.0116), a down-regulation also observed in tissues from hypertrophic human hearts and in hypertrophic and hypertensive primate and rodent models. [25][26][27][28] SERCA2a, a marker of heart failure 29 -31 was not significantly different in the ventricles or atria of either line. It is apparent from the literature that different patterns of dysregulation for hypertrophic markers characterize specific murine models; importantly, although some markers may not be up-regulated in specific models, an increase in ␣-skeletal actin is always observed.…”

Section: Bi-atrial Enlargement Cardiac Hypertrophy and Dilationmentioning

confidence: 77%

Transgenic Mice with Cardiac-Specific Expression of Activating Transcription Factor 3, a Stress-Inducible Gene, Have Conduction Abnormalities and Contractile Dysfunction

Okamoto¹,

Chaves²,

Chen³

et al. 2001

The American Journal of Pathology

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“…It has been hypothesized that the atrial-to-ventricular switch of MHCs observed in these pathophysiological conditions is the result of the rise in intra-atrial pressure, similar to hemodynamic changes observed during postnatal development. 32 Our approach of microarray analysis with simultaneous examination of thousands of genes extends these observations in single genes to a general pattern of regulation toward a ventricular gene program in AF. Central in the changes are genes related to energy metabolism, also reflected in ultrastructural changes occurring during long-term AF that resemble those seen in fetal cardiomyocytes and in hibernating myocardium.…”

mentioning

confidence: 83%

“…11,31 In AF, an atrial-to-ventricular switch has been shown for some individual genes in atrial samples of hypertrophied 32 and cardiomyopathic hearts, 33 eg, contractile protein isoforms like myosin heavy chains. It has been hypothesized that the atrial-to-ventricular switch of MHCs observed in these pathophysiological conditions is the result of the rise in intra-atrial pressure, similar to hemodynamic changes observed during postnatal development.…”

Section: Permanent Af Leads To a Ventricular-and Fetal-like Genomic Smentioning

confidence: 99%

Reprogramming of the Human Atrial Transcriptome in Permanent Atrial Fibrillation

Barth¹,

Merk²,

Arnoldi³

et al. 2005

Circulation Research

186

172

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Abstract-Atrial fibrillation is associated with increased expression of ventricular myosin isoforms in atrial myocardium, regarded as part of a dedifferentiation process. Whether reexpression of ventricular isoforms in atrial fibrillation is restricted to transcripts encoding for contractile proteins is unknown. Therefore, this study compares atrial mRNA expression in patients with permanent atrial fibrillation to atrial mRNA expression in patients with sinus rhythm and to ventricular gene expression using Affymetrix U133 arrays. In atrial myocardium, we identified 1434 genes deregulated in atrial fibrillation, the majority of which, including key elements of calcium-dependent signaling pathways, displayed downregulation. Functional classification based on Gene Ontology provided the specific gene sets of the interdependent processes of structural, contractile, and electrophysiological remodeling. In addition, we demonstrate for the first time a prominent upregulation of transcripts involved in metabolic activities, suggesting an adaptive response to increased metabolic demand in fibrillating atrial myocardium. Ventricular-predominant genes were 5 times more likely to be upregulated in atrial fibrillation (174 genes upregulated, 35 genes downregulated), whereas atrial-specific transcripts were predominantly downregulated (56 genes upregulated, 564 genes downregulated). Overall, in fibrillating atrial myocardium, functional classes of genes characteristic of ventricular myocardium were found to be upregulated (eg, metabolic processes), whereas functional classes predominantly expressed in atrial myocardium were downregulated (eg, signal transduction and cell communication). Therefore, dedifferentiation with adoption of a ventricular-like signature is a general feature of the fibrillating atrium. Key Words: atrial fibrillation Ⅲ gene expression Ⅲ atrial myocardium Ⅲ functional genomics A trial fibrillation (AF), the most common sustained arrhythmia, is associated with extensive structural, contractile, and electrophysiological remodeling, 1 stabilizing AF in the long run. Because current pharmacological treatment of AF is limited by ventricular proarrhythmia and inefficacy to prevent recurrences of AF, understanding the molecular events of these remodeling processes is essential for the development of new targeted therapeutic interventions. Even though knowledge of genes involved in remodeling processes exists on a gene-by-gene basis including transcripts of the extracellular matrix compartment, 2 ion channels, 1,3 and signal transduction molecules, 4 microarray analysis offers a broader and unbiased approach to identify pathophysiologically relevant pathways. Therefore, we performed a systematic functional analysis of gene expression in permanent atrial fibrillation (pmAF) based on information from the Gene Ontology (GO) database to relate expression changes of single transcripts to known remodeling processes.Moreover, atrial fibrillation has been shown to be associated with an atrial-to-ventricular switch by expr...

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Expression of ventricular-type myosin light chain messenger RNA in spontaneously hypertensive rat atria.

Cited by 23 publications

References 30 publications

Differential hypertrophic effects of cardiotrophin-1 on adult cardiomyocytes from normotensive and spontaneously hypertensive rats

Differential hypertrophic effects of cardiotrophin-1 on adult cardiomyocytes from normotensive and spontaneously hypertensive rats

Transgenic Mice with Cardiac-Specific Expression of Activating Transcription Factor 3, a Stress-Inducible Gene, Have Conduction Abnormalities and Contractile Dysfunction

Reprogramming of the Human Atrial Transcriptome in Permanent Atrial Fibrillation

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