Exogenous Cardiac Bridging Integrator 1 Benefits Mouse Hearts With Pre-existing Pressure Overload-Induced Heart Failure

Frontiers in Physiology
Jing LiTingTing Hong

Abstract

Background: Cardiac bridging integrator 1 (cBIN1) organizes transverse tubule (t-tubule) membrane calcium handling microdomains required for normal beat-to-beat contractility. cBIN1 is transcriptionally reduced in heart failure (HF). We recently found that cBIN1 pretreatment can limit HF development in stressed mice. Here, we aim to explore whether cBIN1 replacement therapy can improve myocardial function in continuously stressed hearts with pre-existing HF. Methods: Adult male mice were subjected to sham or transverse aortic constriction (TAC) surgery at the age of 8-10 weeks old. Adeno-associated virus 9 (AAV9) transducing cBIN1-V5 or GFP-V5 (3 × 1010 vg) was administered through retro-orbital injection at 5 weeks post-TAC. Mice were followed by echocardiography to monitor cardiac function until 20 weeks after TAC. Overall survival, heart and lung weight (LW), and HF incidence were determined. In a second set of animals in which AAV9-cBIN1 pretreatment prevents HF, we recorded cardiac pressure-volume (PV) loops and obtained myocardial immunofluorescence imaging. Results: The overall Kaplan-Meir survival of AAV9-cBIN1 mice was 77.8%, indicating a significant partial rescue between AAV9-GFP (58.8%) and sham (100%) treated mice....Continue Reading

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Citations

Mar 7, 2021·International Journal of Molecular Sciences·Jing LiTingTing Hong
May 13, 2021·The Journal of General Physiology·Muhammad S Khan, Robin M Shaw
May 23, 2021·Acta Physiologica·Almudena Val-BlascoMaria Fernández-Velasco

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Methods Mentioned

BETA
electrophoresis

Software Mentioned

PVAN
ImageJ
Matlab
LabChart7

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