Immunohistological and ultrastructural analysis of the intimal thickening in coarctation of human aorta

Objectives: The histological nature and characteristics of aortic coarctati on are not clearly defined, the aim of this study is to analyse intimal thi ckening in aortic coarctation. Methods: In order to characterize the compon ents of intimal thickening in coarctation, narrowed segments of aorta obtai ned after surgery from ten children were examined immunocytochemically and by electron microscopy. Results: Histological analysis of aortic coarctatio n demonstrated a widened subendothelial region with separation of endotheli al cells from the internal elastic lamina. Masson's trichrome staining show ed a marked increase in extracellular matrix and cell numbers in the intima l thickening compared with normal aorta. Cellular component analysis demons trated invagination of the intima by smooth muscle actin-positive cells, wi th a fragmentation of the internal elastic lamina. No proliferating smooth muscle and inflammatory cells were identified in the intima. In order to ch aracterize the smooth muscle cell phenotypes, various smooth muscle cell ma rkers were sought using specific monoclonal antibodies: alpha-smooth muscle actin, smooth muscle-myosin heavy chain, heavy caldesmon, desmin. In moder ate coarcted aorta, at least two distinct smooth muscle phenotypes were ide ntified. In the juxtamedial part of the intima smooth muscle, cells were di fferentiated and expressed all smooth muscle markers; in the subendothelial part of the intimal thickening, the majority of smooth muscle cells expres sed only oc-smooth muscle actin and appeared dedifferentiated. In regions o f marked stenosis, a strong expression of smooth muscle-myosin heavy chain, and heavy caldesmon in the intimal thickening pointed to the presence of r edifferentiated smooth muscle cells, not still expressing desmin. Electron microscopic examination also revealed a variety of smooth muscle cell pheno types in the intimal thickening. In the superficial layer, smooth muscle ce lls appeared to be in the synthetic state, while in the deeper part, both s ynthetic and contractile components were identified. Conclusions: These obs ervations indicated that human coarctation was characterized by intimal rec ruitment of non-proliferating smooth muscle cells with dedifferentiated phe notype. However, the presence of smooth muscle cells with an intermediate p henotype in the narrowest part of the coarctation suggest that the rediffer entiation process could participate in the pathogenesis of aortic coarctati on. (C) 1999 Elsevier Science B.V. All rights, reserved.