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From the Laboratories of Molecular Cardiology (H.J., S.Z., I.M.C.D.) and
Membrane Biology (P.S.T., V.P.), Institute of Cardiovascular Sciences, St
Boniface General Hospital Research Centre, Faculty of Medicine, University of
Manitoba, Winnipeg, Manitoba, Canada.
Correspondence to Ian M.C. Dixon, PhD, Institute of Cardiovascular Sciences, St Boniface General Hospital Research Centre, University of Manitoba, 351 Tache Ave, Winnipeg, Manitoba, Canada R2H 2A6. E-mail iand{at}sbrc.umanitoba.ca
Background—Large transmural
myocardial infarction (MI) leads to maladaptive cardiac remodeling and
places patients at increased risk of congestive heart failure.
Angiotensin II, endothelin, and
Methods and Results—MI was produced in rats by ligation of the
left coronary artery, and Gq
Conclusions—Upregulation of the Gq
© 1998 American Heart Association, Inc.
Basic Science Reports
Expression of Gq
and PLC-ß in Scar and Border Tissue in Heart Failure Due to Myocardial Infarction
1-adrenergic
receptor agonists are implicated in the development of cardiac
hypertrophy, interstitial fibrosis, and heart
failure after MI. Because these agonists are coupled to and
activate Gq protein in the heart, the aim of the
present study was to investigate Gq expression and
function in cardiac remodeling and heart failure after MI. protein
concentration, localization, and mRNA abundance were noted in surviving
left ventricle remote from the infarct and in border and scar tissues
from 8-week post-MI hearts with moderate heart failure.
Immunohistochemical staining localized elevated Gq
expression in the scar and border tissues. Western analysis
confirmed significant upregulation of Gq proteins in
these regions versus controls. Furthermore, Northern analysis
revealed that the ratios of Gq/GAPDH mRNA abundance in
both scar and viable tissues from experimental hearts were
significantly increased versus controls. Increased expression of
phospholipase C (PLC)-ß1 and PLC-ß3
proteins was apparent in the scar and viable tissues after MI versus
controls and is associated with increased PLC-ß1 activity
in experimental hearts. Furthermore, inositol 1,4,5-tris-phosphate is
significantly increased in the border and scar tissues compared with
control values. /PLC-ß pathway
was observed in the viable, border, and scar tissues in post-MI hearts.
Gq and PLC-ß may play important roles in scar
remodeling as well as cardiac hypertrophy and fibrosis of
the surviving tissue in post-MI rat heart. It is suggested that the
Gq/PLC-ß pathway may provide a possible novel target
for altering postinfarct remodeling.
Key Words: proteins • phospholipase • myocardial infarction • heart failure • remodeling
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