ELASTIN EXPRESSION IN A MODEL OF ACUTE ARTERIAL GRAFT-REJECTION

Elastin is an important component of normal blood vessels and the extr acellular matrix of atherosclerotic plaques, but its role in intimal t hickening in the arteries of transplanted organs has not been defined. We have looked at elastin gene expression (by in situ mRNA hybridizat ion) in an animal model using an abdominal aortic transplant between 2 strains of rats disparate for MHC class I antigens. The normal aortic wall of adult rats lacks elastin mRNA. Aortic allografts at 7 days af ter transplantation exhibit increased elastin mRNA in the medial vascu lar smooth muscle cells. This medial elastin mRNA expression is presen t only until 20 days after transplantation, and at later times, only t he juxtaluminal cells of the neointima express elastin mRNA. Stainable elastin is detectable only in regions that previously demonstrated hi gh levels of elastin mRNA. Combined in situ hybridization and immunocy tochemistry reveals that most elastin mRNA-expressing cells in the med ia are alpha-actin-positive smooth muscle cells. In the neointima, ela stin mRNA-expressing cells do not stain with antibodies to either smoo th muscle alpha-actin or macrophage proteins. This cell population may represent a ''synthetic'' phenotype of vascular smooth muscle cell la cking alpha-actin protein. We presume there is immune cell-mediated in jury leading to a vascular smooth muscle cell response and part of the vascular smooth muscle cell response may be increased elastin mRNA ex pression and elastin deposition in the allografts.