The level of endothelial cell (EC) proliferation in normal, mature vessels in most mammals remains poorly defined but in general is reported to be extremely low, if not nonexistent. In fact, until approximately 50 years ago, the predominant view held that ECs lining vessels do not undergo mitosis. However, the advent of tritiated thymidine labeling studies and modifications of the Hautchen preparation permitted direct analysis of EC mitosis in vessels recovered after labeling in vivo (1). In some experimental animals, such as rats, guinea pigs, pigs, and dogs, the tritiated thymidine labeling studies demonstrated 0.1% to 3.0% EC turnover daily (2, 3). Endothelial proliferation rates were correlated with the age of the subject and appeared to decline rapidly after birth with most adult vessel endothelium displaying mitosis in <1% of the cells daily (4). Furthermore, the sites of endothelial replication were not homogenously distributed but appeared to occur in clustered areas nearest vessel bifurcations where flow was disturbed and often turbulent (2). Whether these dividing ECs were unique and possessed proliferative potential that was lacking in other mature endothelium or these focal areas of replicating cells merely represented the sites of greatest vessel injury and endothelial turnover has not yet been determined. It has been well documented that EC division may reach 50% of the cells in the thoracic aorta following experimentally induced hypertension, re-endothelialization of organized clots or injured vessels after arterial denudation, or following experimentally induced vascular constriction (5).

In marked contrast to the slow turnover of ECs in normal vessels, in vitro plating of ECs derived from human or animal vessels is associated with brisk EC proliferation.