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Published on: July 25, 2019
Expression of hyperpolarization-activated cyclic nucleotide-gated channel isoforms in a canine model of atrial
Wei He1, Jian Zhang1, Tianyi Gan1
1Pacing Electrophysiology Division, First Affiliated Hospital of Xinjiang Medical University, Ürümqi, Xinjiang 830054, P.R. China.
Abstract:
The aim of the present study was to analyze the mRNA and protein expression levels of atrial hyperpolarization-activated cyclic nucleotide-gated (HCN) channel isoforms in the left atrial muscle of dogs with multiple organ failure. A total of 14 beagle dogs with multiple organ failure, including seven cases with sinus rhythm and seven cases with atrial fibrillation (AF), underwent surgery to remove a sample of left atrial appendage tissue. The expression levels of a number of HCN channel subtypes were subsequently measured using quantitative polymerase chain reaction and western blot analysis. The mRNA and protein expression levels of HCN2 and HCN4 increased significantly in the AF group when compared with the sinus rhythm group. However, expression of the HCN1 isoform was not detected. Therefore, increased expression levels of HCN2 and HCN4 may be important molecular mechanisms in the pathogenesis of AF, which were associated with differences in patients with valvular heart disease.
Insights
In dogs with multiple organ failure, atrial fibrillation was linked to higher levels of hyperpolarization-activated cyclic nucleotide-gated (HCN) channel 2 and 4. These HCN channel changes may contribute to the development of atrial fibrillation.
Area of Science:
- Cardiology
- Molecular Biology
- Veterinary Medicine
Background:
- Atrial fibrillation (AF) is a common arrhythmia.
- Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels play a role in cardiac rhythm.
- The role of HCN isoforms in AF, particularly in the context of multiple organ failure, requires further investigation.
Purpose of the Study:
- To investigate the mRNA and protein expression of HCN channel isoforms in the left atrial muscle of dogs with multiple organ failure.
- To compare HCN expression levels between dogs with sinus rhythm and those with atrial fibrillation.
Main Methods:
- Analysis of left atrial appendage tissue from 14 beagle dogs with multiple organ failure.
- Quantitative polymerase chain reaction (qPCR) to measure mRNA expression levels.
- Western blot analysis to measure protein expression levels.
Main Results:
- HCN2 and HCN4 mRNA and protein expression levels were significantly increased in dogs with atrial fibrillation compared to those with sinus rhythm.
- HCN1 isoform expression was not detected in any of the samples.
- Increased HCN2 and HCN4 expression may be a molecular mechanism in the pathogenesis of AF.
Conclusions:
- Elevated expression of HCN2 and HCN4 in the left atrium may contribute to the development of atrial fibrillation in dogs with multiple organ failure.
- These findings suggest a potential link between HCN channel expression and AF in the context of systemic disease.
- Further research is warranted to explore the therapeutic implications of targeting HCN channels in AF.
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