Expression of G qα and PLC-β in Scar and Border Tissue in Heart Failure Due to Myocardial Infarction

Abstract

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 α 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 G qα protein in the heart, the aim of the present study was to investigate G qα expression and function in cardiac remodeling and heart failure after MI. Methods and Results —MI was produced in rats by ligation of the left coronary artery, and G qα 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 G qα expression in the scar and border tissues. Western analysis confirmed significant upregulation of G qα proteins in these regions versus controls. Furthermore, Northern analysis revealed that the ratios of G qα /GAPDH mRNA abundance in both scar and viable tissues from experimental hearts were significantly increased versus controls. Increased expression of phospholipase C (PLC)-β 1 and PLC-β 3 proteins was apparent in the scar and viable tissues after MI versus controls and is associated with increased PLC-β 1 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 G qα /PLC-β pathway was observed in the viable, border, and scar tissues in post-MI hearts. G qα and PLC-β 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 G qα /PLC-β pathway may provide a possible novel target for altering postinfarct remodeling.