The adventitia: the outs and ins of vascular disease.

Long before it was established that the adventitia is a major source of vasoactive factors and a pivotal participant in vascular remodeling, it was noted that the changes occurring in the adventitia could be a signal of impending vascular disease, among them marked hypercellularity, increased connective tissue production, and clear signs of inflammation. Various forms of hypertension, atherosclerosis, and vascular injury are characterized by adventitial cell proliferation and increased leukocyte levels in the perivascular space. In 1915, Albutt [1] reported finding inflammatory cells in the perivascular adventitia of atherosclerotic arteries. Almost half a century later, Schwartz and Mitchell [2] showed a positive correlation between the magnitude of adventitial inflammation and the severity of atherosclerosis. However, for more than 30 years, these observations remained a curious, yet peculiar phenomenon that was largely ignored and generally considered irrelevant to homeostasis of the vessel wall. Until recently, doubts persisted that this outer segment of the blood vessel could have far-reaching effects on the vascular wall, including profound changes affecting medial smooth muscle and endothelial cell biology. Over the past decade, however, a few landmark studies illustrated a highly important role for the adventitia in dysfunction, ranging from interference in endothelium-dependent responses to a direct contribution of adventitial myofibroblasts to restenosis. It is our expectation and hope that the reviews and original publications in this issue will shed important new light on an important role for the adventitia in vascular physiology and pathophysiology.