Expression of G(i-2 alpha) and G(s alpha) in myofibroblasts localized to the infarct scar in heart failure due to myocardial infarction

Objective: Patients surviving large transmural myocardial infarction (MI) a re at risk for congestive heart failure with attendant alteration of ventri cular geometry and scar remodeling. Altered G(i-2 alpha) and G(s alpha) pro tein expression may be involved in cardiac remodeling associated with heart failure, however their expression in scar tissue remains unclear. Methods: MI was produced in Sprague-Dawley rats by ligation of the left coronary ar tery. G(i-2 alpha) and G(s alpha) protein concentration, localization and m RNA abundance were noted in surviving left ventricle remote to the infarct, in border and in scar tissues from 8 week post-MI hearts with moderate hea rt failure. Results: We observed a 4.5- and 5.0-fold increase in immunoreac tive G(i-2 alpha) protein concentration occurs in the border and scar regio ns vs. control values, respectively, in 8-week post-MI rat hearts. Similarl y, immunoreactive G(s alpha) protein concentration was increased 3.4- and 8 .2-fold, respectively, in these tissues vs. controls. Double-fluorescence l abeling and phenotyping studies revealed that both G(i-2 alpha) and G(s alp ha) proteins were localized to myofibroblasts in the infarct scar and to vi able myocytes bordering the scar. Northern analysis revealed that the G(i-2 alpha)/GAPDH ratio was increased in both viable and scar regions (1.24- an d 1.85-fold respectively) from experimental hearts when compared to sham-op erated control values when compared to noninfarcted left ventricle, the val ue of this ratio in scar tissue was elevated similar to 1.5 fold. The G(s a lpha)/GAPDH ratio was significantly increased (1.28-fold) only in the scar region vs. control. Conclusion: Our results indicate a marked increase in t he expression of G(i-2 alpha) and G(s alpha) from myofibroblasts of the inf arct scar as well as remnant myocytes bordering the scar in 8-week post-MI rat hearts. We suggest that these changes may be associated with ongoing re modeling in the infarct scar in chronic post-MI phase of this experimental model. (C) 1999 Elsevier Science B.V. All rights reserved.