Abstract：
:Atrial fibrillation (AF) is commonly associated with chronic dilatation of the left atrium, both in human disease and animal models. The immediate signaling enzyme phospholipase C (PLC) is activated by mechanical stretch to generate the Ca2+-releasing messenger inositol(1,4,5)trisphosphate (Ins(1,4,5)P3) and sn-1,2-diacylglycerol (DAG), an activator of protein kinase C subtypes. There is also evidence that heightened activity of PLC, caused by the receptor coupling protein Gq, can contribute to atrial remodelling. We examined PLC activation in right and left atrial appendage from patients with mitral valve disease (VHD) and in a mouse model of dilated cardiomyopathy caused by transgenic overexpression of the stress-activated protein kinase, mammalian sterile 20 like kinase 1 (Mst1) (Mst1-TG). PLC activation was heightened 6- to 10-fold in atria from VHD patients compared with right atrial tissue from patients undergoing coronary artery bypass surgery (CABG) and was also heightened in the dilated atria from Mst1-TG. PLC activation in human left atrial appendage and in mouse left atria correlated with left atrial size, implying a relationship between PLC activation and chronic dilatation. Dilated atria from human and mouse showed heightened expression of PLCbeta1b, but not of other PLC subtypes. PLCbeta1b, but not PLCbeta1a, caused apoptosis when overexpressed in neonatal rat cardiomyocytes, suggesting that PLCbeta1b may contribute to chamber dilatation. The activation of PLCbeta1b is a possible therapeutic target to limit atrial remodelling in VHD patients.
journal_name
J Mol Cell Cardioljournal_title
Journal of molecular and cellular cardiologyauthors
Woodcock EA,Grubb DR,Filtz TM,Marasco S,Luo J,McLeod-Dryden TJ,Kaye DM,Sadoshima J,Du XJ,Wong C,McMullen JR,Dart AMdoi
10.1016/j.yjmcc.2009.08.020subject
Has Abstractpub_date
2009-11-01 00:00:00pages
676-83issue
5eissn
0022-2828issn
1095-8584pii
S0022-2828(09)00361-7journal_volume
47pub_type
杂志文章abstract：:The effect of isoproterenol on mechanical function was studied in the isolated arterially perfused heart of the fetal (21st and 28th day of gestation) and newborn rabbits. The inotropic effect of isoproterenol in the fetus was less than in the newborn. In contrast, myocardial cyclic AMP levels after isoproterenol infu...
journal_title：Journal of molecular and cellular cardiology
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pub_type： 杂志文章,评审
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