Title: Risk and Mechanism for Sudden Cardiac Death in NOS1AP Knockout Mice
Abstract: Recent genome wide association studies have reported that single nucleotide polymorphism (SNP) in NO synthase 1 adaptor protein (NOS1AP) has significantly high association with QT interval and sudden cardiac death (SCD). Following study revealed NOS1AP overexpression shortened action potential duration of ventricular myocyte by decreasing L-type Ca current. However, the risk for SCD in patients with SNP of NOS1AP has not been fully elucidated. The purpose of our study was to clarify the risk of SCD and arrhythmogenicity under several pathological models using NOS1AP knockout mice (KO). Methods: Surface ECG parameter was acquired in KO and wild type (WT) mice. Then several interventions were performed to make pathological models (myocardial infarction (MI), ischemia/reperfusion injury (IR), and transverse aortic constriction (TAC)). Results: QTc was more prolonged in KO mice than WT (46ms vs. 50ms). This QTc difference was abolished by administration of NOS inhibitor (l-NAME). Survival rate after MI and IR were not different between KO and WT mice. After TAC operation, SCD occurred more prominently in KO mice than WT (ratio of SCD: 6/15 vs. 3/16). Sequential ECG recording after TAC exhibited sporadic premature ventricular contractions only in KO mice. Conclusion: NOS1AP regulates QTc via NO production. And the risk of SCD is increased under pressure overload in NOS1AP KO mice but not in infarction or ischemia/reperfusion.
Publication Year: 2010
Publication Date: 2010-09-01
Language: en
Type: article
Indexed In: ['crossref']
Access and Citation
AI Researcher Chatbot
Get quick answers to your questions about the article from our AI researcher chatbot