Intracellular Chloride Accumulation and Subcellular Elemental Distribution During Atrial Fibrillation

Akar, Joseph G.; Everett, Thomas H.; Ho, Ruoya; Craft, Joseph; Haines, David E.; Somlyo, Andrew P.; Somlyo, Avril V.

doi:10.1161/01.cir.0000058462.23347.93

Cited by 32 publications

(24 citation statements)

References 40 publications

(48 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

Section: Generalized Transcriptional Downregulation In Permanent Af mentioning

confidence: 99%

“…In fact, after an initial increase, steady-state calcium levels begin to decrease as early as 30 minutes after initiation of AF and normalize within the first 48 hours. 27 Moreover, Ausma and coworkers 28 demonstrated decreased steady-state calcium levels after 16 weeks of AF in goats. Likewise, isolated Individual measurements for fibrillin 1 and TGF-␤ receptor 2 in all tissue SR (ϭblack columns) and pmAF specimens (ϭwhite columns), illustrating that downregulation of these genes was not restricted to the patient with Marfan syndrome (AF-1; first column), but common to all pmAF patients.…”

Section: Generalized Transcriptional Downregulation In Permanent Af mentioning

confidence: 99%

See 1 more Smart Citation

Reprogramming of the Human Atrial Transcriptome in Permanent Atrial Fibrillation

Barth¹,

Merk²,

Arnoldi³

et al. 2005

Circulation Research

184

172

View full text Add to dashboard Cite

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...

show abstract

Section: Generalized Transcriptional Downregulation In Permanent Af mentioning

confidence: 99%

Section: Generalized Transcriptional Downregulation In Permanent Af mentioning

confidence: 99%

Reprogramming of the Human Atrial Transcriptome in Permanent Atrial Fibrillation

Barth¹,

Merk²,

Arnoldi³

et al. 2005

Circulation Research

184

172

View full text Add to dashboard Cite

show abstract

“…A decrease in peak I Na activity was reported in remodeled canine [20], but not goat atria [21]. Interestingly, Na i was shown to be reduced in canine atrial cells after 48 h of atrial-tachypacing [22]. …”

Section: Electrophysiology Of Late Sodium Currentmentioning

confidence: 99%

Role of Late Sodium Channel Current Block in the Management of Atrial Fibrillation

Burashnikov

Antzelevitch

2012

Cardiovasc Drugs Ther

View full text Add to dashboard Cite

The anti-arrhythmic efficacy of the late sodium channel current (late INa) inhibition has been convincingly demonstrated in the ventricles, particularly under conditions of prolonged ventricular repolarization. The value of late INa block in the setting of atrial fibrillation (AF) remains poorly investigated. All sodium channel blockers inhibit both peak and late INa and are generally more potent in inhibiting late vs. early INa. Selective late INa block does not prolong the effective refractory period (ERP), a feature common to practically all anti-AF agents. Although the late INa blocker ranolazine has been shown to be effective in suppression of AF, it is noteworthy that at concentrations at which it blocks late INa in the ventricles, it also potently blocks peak INa in the atria, thus causing rate-dependent prolongation of ERP due to development of post-repolarization refractoriness. Late INa inhibition in atria is thought to suppress intracellular calcium (Cai)-mediated triggered activity, secondary to a reduction in intracellular sodium (Nai). However, agents that block late INa (ranolazine, amiodarone, vernakalant, etc) are also potent atrial-selective peak INa blockers, so that the reduction of Nai loading in atrial cells by these agents can be in large part due to the block of peak INa. The impact of late INa inhibition is reduced by the abbreviation of the action potential that occurs in AF patients secondary to electrical remodeling. It stands to reason that selective late INa block may contribute more to inhibition of Cai-mediated triggered activity responsible for initiation of AF in clinical pathologies associated with a prolonged atrial APD (such as long QT syndrome). Additional studies are clearly needed to test this hypothesis.

show abstract

“…An increase of intracellular chloride ions concentration was observed experimentally during atrial fibrillation in dogs [37], which was associated with ion channels remodeling during atrial fibrillation. An increased concentration of chloride in the extracellular environment (resulting from environmental pollution) could intensify this phenomenon.…”

Section: Discussionmentioning

confidence: 93%

The Content of Elements in Rainwater and its Relation to the Frequency of Hospitalization for Atrial Fibrillation in Opole Voivodship, Poland, During 2000–2002

Tubek

Bunio

Szyguła

et al. 2010

Biol Trace Elem Res

View full text Add to dashboard Cite

The elemental composition of rainwater is a suitable indirect indicator of the presence of chemical elements in airborne dust. As such, rainwater is considered a suitable monitor for environmental or natural pollution. The yearly content of chemical elements in rainwater may be considered a good indicator for determining the influence of these environmental factors on human body. We decided to investigate the relationship between chemical elements in rainwater and the frequency of hospitalizations for atrial fibrillation (I48, ICD10) on the population of the region of Opole Voivodship, Poland during the years 2000-2002. The voivodship or province has a population of one million and is divided into 12 counties that have between 44,000 and 151,000 inhabitants. We calculated the yearly average number of hospitalizations by reasons of atrial fibrillation per 10,000 inhabitants in particular counties. The average content of the chosen chemical elements in kilograms per hectare per year was calculated for each county individually and the data evaluated by means of Spearman's correlation coefficient. There is a high positive correlation between chromium in rainwater and hospital admissions for atrial fibrillation (r = 0.62) and mild positive correlation with cadmium (r = 0.57), lead (r = 0.57), zinc (r = 0.50), and chloride (r = 0.48). There are no significant differences between male and female patients. The biological activities of these elements, which may include enhanced adrenergic stimulation, remodeling of calcium or other ion channels, or the cytotoxic effects of hexavalent chromium may explain the positive correlations here reported.

show abstract

Intracellular Chloride Accumulation and Subcellular Elemental Distribution During Atrial Fibrillation

Cited by 32 publications

References 40 publications

Reprogramming of the Human Atrial Transcriptome in Permanent Atrial Fibrillation

Reprogramming of the Human Atrial Transcriptome in Permanent Atrial Fibrillation

Role of Late Sodium Channel Current Block in the Management of Atrial Fibrillation

The Content of Elements in Rainwater and its Relation to the Frequency of Hospitalization for Atrial Fibrillation in Opole Voivodship, Poland, During 2000–2002

Contact Info

Product

Resources

About