EXPRESSION OF G(Q-ALPHA) AND PLC-BETA IN SCAR AND BORDER TISSUE IN HEART-FAILURE DUE TO MYOCARDIAL-INFARCTION

Background-Large transmural myocardial infarction (MI) leads to malada ptive cardiac remodeling and places patients at increased risk of cong estive heart failure. Angiotensin II, endothelin, and alpha(1)-adrener gic receptor agonists are implicated in the development of cardiac hyp ertrophy, interstitial fibrosis, and heart failure after MI. Because t hese agonists are coupled to and activate G(q alpha) protein in the he art, the aim of the present study was to investigate G(q alpha) expres sion and function in cardiac remodeling and heart failure after MI. Me thods and Results-MI was produced in rats by ligation of the left coro nary artery, and G(q alpha) protein concentration, localization, and m RNA abundance were noted in surviving left ventricle remote from the i nfarct and in border and scar tissues from 8-week post-MI hearts with moderate heart failure. Immunohistochemical staining localized elevate d G(q alpha) expression in the scar and border tissues. Western analys is confirmed significant upregulation of G(q alpha) proteins in these regions versus controls. Furthermore, Northern analysis revealed that the ratios of G(q alpha)/GAPDH mRNA abundance in both scar and viable tissues from experimental hearts were significantly increased versus c ontrols. Increased expression of phospholipase C (PLC)-beta(1) and PLC -beta(3) proteins was apparent in the scar and viable tissues after MI versus controls and is associated with increased PLC-beta(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(q alpha)/PLC-beta pa thway was observed in the viable, border, and scar tissues in post-MI hearts. G(q alpha) and PLC-beta may play important roles in scar remod eling as well as cardiac hypertrophy and fibrosis of the surviving tis sue in post-MI rat heart. It is suggested that the G(q alpha)/PLC-beta pathway may provide a possible novel target for altering postinfarct remodeling.