Extracellular matrix of the human aortic media: an ultrastructural histochemical and immunohistochemical study of the adult aortic media

Abstract

Aortic distensability is the key to normal aortic function and relates to the lamellar unit in the media. However, the organization of the extracellular matrix components in these lamellar units, which are largely responsible for the distensability, is insufficiently known, especially in the human. We therefore performed a detailed ultrastructural analysis of these components. Thoracic aortas of 56 individuals (age 45-74 years), none of whom suffered from aortic disease, were studied by immunoelectron microscopy of elastin, collagen types I, III, IV, V, and VI, fibronectin, and fibrillin-1, and by ultrastructural histochemistry of proteoglycans, which were further characterized by enzymatic digestion. The elastic lamellae were closely associated with thick collagen fibers containing types I, III, and V collagen. Between these collagen fibers, numerous complex, circumferentially oriented streaks of elastin protruded from the lamellae. In contrast to what is usually reported in the aortas of experimental animals, the smooth muscle cells preferentially adhered to these ill-defined streaks rather than directly to the solid lamellae. Fibrillin-1- and type VI collagen-containing bundles of microfibrils (oxytalan fibers) were also involved in the smooth muscle cell-elastin contact. The smooth muscle cells were invested by basal lamina-like layers connecting them to each other as well as to the oxytalan fibers. Unexpectedly, these layers were abundantly labeled by anti-fibronectin, whereas type IV collagen, a specific basement membrane component, was mainly found in larger, flocculent deposits. The proteoglycans present were collagen-associated dermatan sulfate proteoglycan, cell-associated heparan sulfate proteoglycan, and interstitial chondroitin sulfate proteoglycan. Our observations demonstrate that the extracellular matrix in the human aorta is extremely complex and therefore differs from most descriptions based on experimental animals. They serve as reference for future studies on aortic diseases, such as aneurysmas and dissections.