Normally, blood vessels are quiescent structures that fulfill their crucial function delivering blood to tissues and organs throughout the body with remarkable efficiency over the course of the entire normal lifespan. This is accomplished through interactions among a wide variety of regulatory systems that control the structure and function of the vasculature. The endothelium not only makes up the innermost layer of all blood vessels and provides a nonthrombogenic surface, but it also produces awide variety of vascular and growth regulatory signals and participates in repair, remodeling, and regeneration of the vasculature. The endothelium normally exhibits a very slow turnover, with a half-life of several years; however, in response to arterial injury and forms of pathological stress, widespread damage to the endothelium necessitates efficient mechanisms of repair and regeneration. Understanding the endogenous mechanisms that protect and repair this crucial layer may form the basis for new therapeutic strategies for the treatment of vascular diseases.

LOCAL VERSUS SYSTEMIC MECHANISMS OF VASCULAR REPAIR

Until quite recently, repair of the damaged endothelium was thought to occur largely from the migration and proliferation of nearby undamaged endothelial cells (ECs) (1), and the regeneration of new blood vessels was believed to be mainly through the sprouting of ECs from preexisting blood vessels. However, several observations challenged this concept, beginning as early as 1963, when it was found that Dacron patches that were not contiguous with the vascular endothelium could become efficiently endothelialized (2), presumably by seeding from circulating ECs or endothelial progenitor cells (EPCs). In later studies using a genetic tag, it could be shown that the colonizing cells were of bone marrow (BM) origin (3).