Abstract
Abstract 240: Mistrafficking of Integrin β1d Contributes to Ca2+handling Disorder and Catecholaminergic Polymorphic Ventricular Tachycardia Under Cardiac Stress
Circulation research, Vol.125(Suppl_1)
08/02/2019
DOI: 10.1161/res.125.suppl_1.240
Abstract
Background:
RyR2 hyper-phosphorylation has been identified as a contributing mechanism to arrhythmogenesis. The integrin β1D colocalized with RyR2 and stabilized phosphorylation of RyR2, which maintains the function of the RyR2 channel. Our objective is to investigate whether the alteration of β1D integrin is a novel mechanism to arrhythmogenesis under cardiac stress.
Methods and Results:
Using transgenic mouse model β1D-/- mice, which results in more uncoupling of β1D and RyR2, showed significantly increased the RyR2 ser2808 phosphorylation and Ca2+handling disorder and CPVT. Translocation of the β1D and uncoupling with RyR2 were discovered in the cardiac disease in human and animal model, instead of decreased β1D. KIF5B mediated β1D redistributed from the center to the periphery with hyper-phosphorylation of ser2808 and Ca2+handling dysfunction.
Conclusions:
These results discover that translocation of β1D and disassociation from RyR2, which leads to hyper-phosphorylation of the RyR2 ser2808, is a novel pathway to trigger CPVTunder cardiac disease.
Details
- Title: Subtitle
- Abstract 240: Mistrafficking of Integrin β1d Contributes to Ca2+handling Disorder and Catecholaminergic Polymorphic Ventricular Tachycardia Under Cardiac Stress
- Creators
- Yihui Wang - Fuwai Hosp, Beijing, ChinaChunyan Li - Fuwai Hosp, Beijing, ChinaShi Ling - Haerbin Med Univ, Haerbin, ChinaLong-Sheng Song - University of IowaShiHua Zhao - Fuwai Hosp, Beijing, China
- Resource Type
- Abstract
- Publication Details
- Circulation research, Vol.125(Suppl_1)
- DOI
- 10.1161/res.125.suppl_1.240
- ISSN
- 0009-7330
- eISSN
- 1524-4571
- Language
- English
- Date published
- 08/02/2019
- Academic Unit
- Cardiovascular Medicine; Internal Medicine; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology
- Record Identifier
- 9984297353002771
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