ENDOTHELIN-1 IMMUNOREACTIVITY AND MESSENGER-RNA IN THE TRANSPLANTED HUMAN HEART

Endothelin-l (ET-1) is a al-residue peptide produced by endothelial ce lls and possesses a wide range of biological activities, including vas oconstriction, mitogenesis, and inotropic effects on the heart. The ai m of the present study was to determine the cellular localization of E T-1 immunoreactivity and mRNA in routine endomyocardial biopsy specime ns of transplanted human hearts, and to correlate the findings with th e associated histological changes, Multiple-step paraffin sections of 72 biopsy samples were immunostained with antiserum to ET-1 and von Wi llebrand factor (factor VIII) using the avidin-biotin-peroxidase compl ex method, ET-1 immunoreactivity was localized to vascular and endocar dial endothelial cells, as well as to cardiomyocytes. The pattern of e ndothelial cell immunostaining with the ET-1 antiserum was similar to that of factor Vm, Previous biopsy sites and areas of granulation tiss ue appeared to have greater ET-1 immunoreactivity, particularly in sec tions immunostained with the ET-1 antiserum. There was a significant c orrelation between the presence of ET-1 immunoreactivity and fibrosis or granulation tissue in the biopsy specimens (P<0.03), There was no c orrelation between ET-1 immunoreactivity and the presence of cellular infiltrate, definitive rejection, or Quilty effect, In situ hybridizat ion with radio-labeled RNA probes revealed expression of ET-1 mRNA in endothelial cells and myocytes, also in association with granulation t issue and fibrosis, No cellular reactivity was present in control sect ions stained with the ET-1 antiserum preadsorped with its synthetic pe ptide, The findings suggests a possible role for ET-1 in vascular rege neration and angiogenesis following myocardial injury.