Identification of Fibrillins as a Major Component of Coronary Atherosclerotic Plaques

Abstract

Fibrillins are two distinct 350 kD RGD-containing glycoproteins found in microfibrils in the extracellular matrix. Fibrillin-containing microfibrils are required for elastic fiber formation and serve as an anchor for protein binding via β1 and/or αvβ3 receptors. Fibrillin-1 is causally linked to Marfan’s syndrome, which is in part characterized by disruption of the aortic media. Fibrillin-2 is causally linked to congenital contractural arachnodactyly, which is rarely characterized by cardiovascular symptoms. We hypothesized that fibrillins might be present in coronary atherosclerotic plaques and contribute to plaque stability. To test this, we examined the expression of fibrillins-1 and -2 in human coronary arteries and coronary atherectomies. Positive staining for fibrillin-1 and fibrillin-2 proteins was observed by immunochemistry in 95% of the specimens. Fibrillin-1 was localized to the plaque, adventitia, and endothelial cells. Fibrillin-2 stained diffusely in the adventitia and focally in the plaque. Neither fibrillin was abundant in the media. Substantial differences between the amount and localization of histologically stained elastic fibers and fibrillin immunohistochemical staining were noted. By in situ hybridization, fibrillin-1 mRNA was localized to smooth muscle cells, endothelial cells, and fibroblasts. In spite of the presence of fibrillin-2 antigen by immunohistochemistry, fibrillin-2 mRNA was not detected by in situ hybridization. These data implicate fibrillins as important components of the atherosclerotic plaque. Fibrillins may contribute to plaque stability and act as binding sites for other macromolecules within the atherosclerotic lesion.