Expression of Gq alpha and PLC-beta in scar and border tissue in heart failure due to myocardial infarction.
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 alpha1-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 alpha protein in the heart, the aim of the present study was to investigate Gq alpha expression and function in cardiac remodeling and heart failure after MI.


RESULTS
MI was produced in rats by ligation of the left coronary artery, and Gq alpha 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 alpha expression in the scar and border tissues. Western analysis confirmed significant upregulation of Gq alpha proteins in these regions versus controls. Furthermore, Northern analysis revealed that the ratios of Gq alpha/GAPDH mRNA abundance in both scar and viable tissues from experimental hearts were significantly increased versus controls. Increased expression of phospholipase C (PLC)-beta1 and PLC-beta3 proteins was apparent in the scar and viable tissues after MI versus controls and is associated with increased PLC-beta1 activity in experimental hearts. Furthermore, inositol 1,4,5-tris-phosphate is significantly increased in the border and scar tissues compared with control values.


CONCLUSIONS
Upregulation of the Gq alpha/PLC-beta pathway was observed in the viable, border, and scar tissues in post-MI hearts. Gq alpha and PLC-beta 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 alpha/PLC-beta pathway may provide a possible novel target for altering postinfarct remodeling.
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Laboratory of Molecular Cardiology, Institute of Cardiovascular Sciences, St Boniface General Hospital Research Centre, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Zhao
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Tappia
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Panagia
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Dixon
I M
IM
D000818:Animals; D002921:Cicatrix / Q000378:metabolism; D003094:Collagen / Q000032:analysis; D005355:Fibrosis / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006333:Heart Failure / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D017379:Hypertrophy, Left Ventricular / Q000209:etiology / Q000378:metabolism; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D009203:Myocardial Infarction / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism*; D054799:Phospholipase C beta; D051381:Rats; D017207:Rats, Sprague-Dawley; D010738:Type C Phospholipases / Q000378:metabolism*; D015854:Up-Regulation
D007527:Isoenzymes; D003094:Collagen; D010738:Type C Phospholipases; D054799:Phospholipase C beta; C518035:Plcb1 protein, rat; C518041:Plcb3 protein, rat; D019204:GTP-Binding Proteins