Abstract 19074: NPPA Overexpression in Mice Increases Susceptibility to Atrial Fibrillation
Abstract only Introduction: Mutations in natriuretic peptide precursor A (NPPA) gene, which encodes atrial natriuretic peptide (ANP), have been linked with familial atrial fibrillation (AF). Although the precise mechanism by which NPPA mutations cause AF remains unclear, a shortening of the atrial a...
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Published in | Circulation (New York, N.Y.) Vol. 126; no. suppl_21 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
20.11.2012
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Online Access | Get full text |
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Summary: | Abstract only
Introduction:
Mutations in natriuretic peptide precursor A (NPPA) gene, which encodes atrial natriuretic peptide (ANP), have been linked with familial atrial fibrillation (AF). Although the precise mechanism by which NPPA mutations cause AF remains unclear, a shortening of the atrial action potential was demonstrated in an isolated rat heart model. Here, we overexpressed NPPA in a mouse model testing the hypothesis that these mice would be more susceptible to AF.
Methods:
A triple FLAG-tag (FLAG) was fused in-frame with the 3’ end of the either the wild-type (WT) human NPPA (WT-NPPA-FLAG) cDNA or the mutant NPPA peptide containing the COOH-terminal 12 amino acid extension (mut-NPPA-FLAG) isolated from individuals with familial AF. The FLAG-tag does not diminish NPPA biological activity. The expression of the mutated protein was confirmed by measuring mRNA by polymerase-chain reaction (PCR). We used transesophageal atrial pacing (15 second bursts from 50 to 15 ms) to assess inducibility and duration of AF.
Results:
Serial weekly transesophageal pacing starting at 16 weeks of age was performed in WT-NPPA-FLAG and mut-NPPA-FLAG mice. Mut-NPPA-FLAG mice had inducible AF at 16 weeks of age in 61±0.1% compared to WT-NPPA-FLAG (n=6 mice, P<0.05). In addition, induced AF was longer lasting in the mut-NPPA-FLAG as compared to WT (AF burden: 19.2±2.9 [mut] sec vs. 12±4.1 s [WT], P<0.05).
Conclusions:
We show that humanized NPPA overexpression mice are more susceptible to AF with longer AF episodes compared with WT using esophageal pacing. |
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ISSN: | 0009-7322 1524-4539 |
DOI: | 10.1161/circ.126.suppl_21.A19074 |