Journal article
The atypical 'b' splice variant of phospholipase Cβ1 promotes cardiac contractile dysfunction
DR Grubb, B Crook, Y Ma, J Luo, HW Qian, XM Gao, H Kiriazis, XJ Du, P Gregorevic, EA Woodcock
Journal of Molecular and Cellular Cardiology | ELSEVIER SCI LTD | Published : 2015
Abstract
The activity of the early signaling enzyme, phospholipase Cβ1b (PLCβ1b), is selectively elevated in diseased myocardium and activity increases with disease progression. We aimed to establish the contribution of heightened PLCβ1b activity to cardiac pathology. PLCβ1b, the alternative splice variant, PLCβ1a, and a blank virus were expressed in mouse hearts using adeno-associated viral vectors (rAAV6-FLAG-PLCβ1b, rAAV6-FLAG-PLCβ1a, or rAAV6-blank) delivered intravenously (IV). Following viral delivery, FLAG-PLCβ1b was expressed in all of the chambers of the mouse heart and was localized to the sarcolemma. Heightened PLCβ1b expression caused a rapid loss of contractility, 4-6weeks, that was full..
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Awarded by National Health and Medical Research Council
Funding Acknowledgements
None of the authors has any conflicts of interest in relation to the work described. This work was supported by Grants from the Australian National Health and Medical Research Council (NHMRC) #1002328, #10007712, #1022678. EAW, XJD and PG are Fellows of the NHMRC #586621, #1043026, #1046782 respectively. Support was received from the Victorian Government's Operational Infrastructure Support Program, and from a Commercialization Grant provided by the Baker IDI Heart and Diabetes Institute.