VASCULAR SMOOTH-MUSCLE ALPHA-ACTIN EXPRESSION AS AN INDICATOR OF PARENCHYMAL-CELL REPROGRAMMING IN CARDIAC ALLOGRAFTS

Background. In addition to transplant-associated vascular sclerosis, c ardiac allografts also may be vulnerable to a previously unrecognized aspect of remodeling involving reactivation of fetal structural genes in the adult heart, Methods. Vascular smooth muscle (VSM) alpha-actin is encoded by a gene that normally is repressed in the ventricle durin g late gestation. Immunohistochemical analysis of accepted mouse cardi ac allografts was performed to determine whether this fetal actin was reexpressed after transplant. Results. VSM alpha-actin was detected wi thin 30 days after transplant throughout the allograft myocardium, whe re it frequently exhibited a distinct periodicity suggestive of protei n localization im sarcomeres. By 90 days after transplant, VSM alpha-a ctin filaments specifically accumulated in the left ventricular endoca rdium. Donor hearts and isografts did not express myocardial VSM alpha -actin, indicating that fetal gene activation was linked to chronic re jection. Conclusion. The results indicate that chronic rejection is as sociated with fetal muscle gene activation, which may facilitate paren chymal cell remodeling and impair graft sanction.