Beyond the Adventitia

Abstract

See related article, pages 541–549 The anatomy of the arterial wall has traditionally been divided into 3 distinct regions, forming concentric layers surrounding the blood vessel lumen. The intima, consisting of a single layer of endothelial cells in direct contact with the lumen; the media, containing layers of smooth muscle cells and extracellular elastin fibers; and the adventitia, composed largely of collagen and other extracellular matrix protein but also containing fibroblasts, inflammatory cells, and a separate microvasculature. The earliest studies on the role of inflammation in the pathogenesis of atherosclerosis focused on the role of endothelial and smooth muscle cells in disease progression; ie, the cell types that reside within the inner arterial layers.1 Some of the earliest observations demonstrated that that an upregulation of adhesion molecules on the endothelial surface initiates the disease process, resulting in the recruitment of monocytes into the vessel wall. More advanced lesions are characterized by the migration and proliferation of the smooth muscle cells, which further contribute to the remodeling of the arterial microstructure. The accumulation of cells and matrix proteins within the developing plaque leads to a lumen narrowing and an altered intimal microenvironment. The adventitia, on the other hand, has historically been regarded as a minor participant in the disease process, and its functional role in plaque formation and development have largely been overlooked. However, the inflammatory response that occurs in the setting of atherosclerosis clearly involves adventitia. Contributions of adventitia-derived inflammatory cells, cytokines, and microvasculature likely contribute significantly in many different vascular disease states.2,3 The involvement of the adventitia in vascular pathology suggest that there is an “outside-in” component to atherosclerosis that is synergistic with the traditional “inside-out” view of atherogenesis. However, arteries are obviously contained within surrounding tissue which, in the case of most vascular beds, is …