ABSTRACT
The normal blood vessel is a complex structure composed of three concentric tunics, the tunica intima, tunica media and tunica adventitia (Figure 26.1). The intima, located at the blood vessel wall-lumen interface, is lined by a single layer of endothelial cells supported by a basement membrane, below which resides a sparse layer of vascular smooth muscle cells.1 The media, located in the middle of the blood vessel wall, consists of smooth muscle cells in lamellar units bound by elastic bands or lamina. The contraction and relaxation of these units allow the artery to constrict or dilate, regulating bloodflow.1 The adventitia, located at the outer layer of the blood vessel, is composed of a loose fibrous network of fibroblasts. The vessels that nourish the blood vessel wall and the nerves that supply neural control are also found in the adventitia.1 The physical continuity of these cells and tissues provides structural integrity to the blood vessel wall while also maintaining homeostasis through biochemical regulation. The complexity of this system renders it extremely sensitive to inflammation, injury or infection and susceptible to significant complications after mechanical manipulation. Angioplasty, 2-4 arteriovenous shunts and fistulae5-7 and organ transplantation, 8 may bypass or treat blood vessel obstructions but they also elicit a sequence of events that induces inflammation, stimulates smooth muscle cell proliferation and culminates in intimal hyperplasia and luminal occlusions. 9, 10
The vascular endothelium is central to understanding vascular biology and critical to maintaining vascular health. The endothelial monolayer that normally lines blood vessels forms a continuous, selectively permeable, thromboresistant surface that regulates local biology to prevent luminal obstructions and ensure uninterrupted distal bloodflow and adequate distal tissue perfusion.11 This level of control is achieved throughout the blood vessel by an array of endothelial cellderived biologically active compounds that regulate virtually every aspect of vascular biology, including thrombosis, vasomotor tone, smooth muscle cell
proliferation and migration, lipid infiltration, and leukocyte adhesion or diapedesion. 10, 12-16 Endothelialstate and cell density determine what compounds will be secreted. While confluence breeds quiescence, monolayer disruption signals growth promotion and accompanying phenomena. 17-21 Asa natural consequence of these observations, many have tried to isolate and infuse single endothelial products to regulate vascular disease, 22-26 and when this has failed, to restore denuded or repair dysfunctional endothelium. 27-29 As a result of these studies, several questions have arisen. Must one recapitulate the ordered architecture of the blood vessel to restore endothelial health? Might structure and function be defined as a continuum, so that restoration of only part of the structure is required for restoration of part of the function? Does one need to completely reconstruct a blood vessel or can one find an intermediate state that will restore health, and does this intermediate state necessitate that we place the cells where they would naturally reside or simply in direct contact with the blood vessel?
