Loss of the Normal Epicardial to Endocardial Gradient of cftr mRNA Expression in the Hypertrophied Rabbit Left Ventricle

Wong, Kevin R.; Trezise, A. E. O.; Crozatier, Bertrand; Vandenberg, Jamie I.

doi:10.1006/bbrc.2000.3754

Cited by 12 publications

(6 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Differentially expressed genes in cardiac tissue derived from patients with different health conditions are summarized in Error! Reference source not found.. We confirmed CFTR [106,107] and KCNJ11 [108] downregulation in HF as well as TRPC6 [12] upregulation in DCM. Interestingly, among the MSC differentially expressed between AF and SR at the whole tissue level (Figure 6), none recurred in HAFprim (Error!…”

Section: Msc Mrna Expression In Human Cardiac Health and Diseasesupporting

confidence: 73%

TREK-1 knock-down in human atrial fibroblasts leads to a myofibroblastic phenotype: a role in phenoconversion and over-view of mechano-sensitive channel mRNA expression in cardiac diseases

Darkow

Yusuf

Rajamani

et al. 2022

Preprint

View full text Add to dashboard Cite

Cardiac cell mechanical environment changes on a beat-by-beat basis and also in the course of various cardiac diseases. Cells sense and adapt to such mechanical cues via specialized mecha-no-sensors mediating adaptive signaling cascades. Here, we report TREK-1 mRNA expression and activity in human atrial fibroblasts and reveal a cross talk between TREK-1 and fibroblast phenoconversion. With the aim to reveal additional candidates underlying mechano-transduction relevant to cardiac diseases, we investigated mechano-sensitive ion channels (MSC) mRNA ex-pression in diseased and non-diseased human hearts. Our results showed higher TREK-1 expression and activity in fibroblasts compared to myo-fibroblasts and we found that TREK-1 down-regulation leads a more myofibroblastic phenotype suggesting a role for this mechano-sensor in phenoconversion. In addition, TREK-1 is preferen-tially expressed in the left atrium compared to the right one and its expression is not significantly changed when fibroblasts from patients in sinus rhythm vs. sustained atrial fibrillation are com-pared. At the whole-heart level, numerous MSC were differentially expressed between atrial and ventricular or between non-diseased and diseased tissue samples. Thus, we identify atrial fibroblast-specific TREK-1 expression and activity and reveal a role of TREK-1 in atrial fibroblast pheno-conversion. We also provide a comprehensive overview of cardiac MSC mRNA expression in atrial and ventricular tissue from diseased and non-diseased patients, identifying potential novel candidates underlying mechanotransduction in cardiac diseases.

show abstract

Section: Msc Mrna Expression In Human Cardiac Health and Diseasesupporting

confidence: 73%

TREK-1 knock-down in human atrial fibroblasts leads to a myofibroblastic phenotype: a role in phenoconversion and over-view of mechano-sensitive channel mRNA expression in cardiac diseases

Darkow

Yusuf

Rajamani

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…More importantly, late I Na is significantly increased both in an experimental heart failure model (127) and in patients (126); the substantial inward current during the plateau phase causes failure of repolarization and decreases its homogeneity, providing substrate for reentry arrhythmias. In rabbit and human ventricular muscle, downregulation and change of the transmural expression pattern of CFTR Cl À channels was observed (906) in the hypertrophied heart. Connexin 43 protein downregulation and its lateralization delay impulse conduction and can enhance anisotropic impulse propagation (878), further contributing to substrate generation for arrhythmias.…”

Section: Remodeling In Heart Failurementioning

confidence: 98%

Cardiac transmembrane ion channels and action potentials: cellular physiology and arrhythmogenic behavior

Varró

Tomek

Nagy

et al. 2021

Physiological Reviews

121

View full text Add to dashboard Cite

Cardiac arrhythmias are among the leading causes of mortality. They often arise from alterations in the electrophysiological properties of cardiac cells, and their underlying ionic mechanisms. It is therefore critical to further unravel the patho-physiology of the ionic basis of human cardiac electrophysiology in health and disease. In the first part of this review, current knowledge on the differences in ion channel expression and properties of the ionic processes that determine the morphology and properties of cardiac action potentials and calcium dynamics from cardiomyocytes in different regions of the heart are described. Then the cellular mechanisms promoting arrhythmias in congenital or acquired conditions of ion channel function (electrical remodelling) are discussed. The focus is human relevant findings obtained with clinical, experimental and computational studies, given that interspecies differences make the extrapolation from animal experiments to the human clinical settings difficult. Deepening the understanding of the diverse patholophysiology of human cellular electrophysiology will help developing novel and effective antiarrhythmic strategies for specific subpopulations and disease conditions.

show abstract

“…Using in situ mRNA hybridization in a combined pressure and volume overload model of heart failure in the rabbit, Wong et al found that the normal epicardial to endocardial gradient of CFTR mRNA expression is reversed due to a significant decrease in epicardial expression of CFTR mRNA in the rabbit left ventricle (164). A posttranslational change in CFTR expression could be responsible for this phenomenon (39).…”

Section: Phenotypic Study Of Cardiac Channelsmentioning

confidence: 99%

Phenomics of Cardiac Chloride Channels

Duan

2013

Comprehensive Physiology

View full text Add to dashboard Cite

Forward genetic studies have identified several chloride (Cl−) channel genes, including CFTR, ClC-2, ClC-3, CLCA, Bestrophin, and Ano1, in the heart. Recent reverse genetic studies using gene targeting and transgenic techniques to delineate the functional role of cardiac Cl− channels have shown that Cl− channels may contribute to cardiac arrhythmogenesis, myocardial hypertrophy and heart failure, and cardioprotection against ischemia reperfusion. The study of physiological or pathophysiological phenotypes of cardiac Cl− channels, however, is complicated by the compensatory changes in the animals in response to the targeted genetic manipulation. Alternatively, tissue-specific conditional or inducible knockout or knockin animal models may be more valuable in the phenotypic studies of specific Cl− channels by limiting the effect of compensation on the phenotype. The integrated function of Cl− channels may involve multiprotein complexes of the Cl− channel subproteome. Similar phenotypes can be attained from alternative protein pathways within cellular networks, which are influenced by genetic and environmental factors. The phenomics approach, which characterizes phenotypes as a whole phenome and systematically studies the molecular changes that give rise to particular phenotypes achieved by modifying the genotype under the scope of genome/proteome/phenome, may provide more complete understanding of the integrated function of each cardiac Cl− channel in the context of health and disease.

show abstract

Loss of the Normal Epicardial to Endocardial Gradient of cftr mRNA Expression in the Hypertrophied Rabbit Left Ventricle

Cited by 12 publications

References 30 publications

TREK-1 knock-down in human atrial fibroblasts leads to a myofibroblastic phenotype: a role in phenoconversion and over-view of mechano-sensitive channel mRNA expression in cardiac diseases

TREK-1 knock-down in human atrial fibroblasts leads to a myofibroblastic phenotype: a role in phenoconversion and over-view of mechano-sensitive channel mRNA expression in cardiac diseases

Cardiac transmembrane ion channels and action potentials: cellular physiology and arrhythmogenic behavior

Phenomics of Cardiac Chloride Channels

Contact Info

Product

Resources

About