Role Of Endothelial Integrity In Atherosclerosis

The current view of the pathogenesis of atherosclerotic lesions stresses loss of endothelial integrity as a major event leading to the three major events in lesion formation. ..accumulation of smooth muscle cells, accumulation of lipid and accumulation of platelets. Recent advances in endothelial biology, however, suggest that frank denudation may not exist. Our kinetic studies of small wounds to endothelium both in vivo and in vitro demonstrate the ability of the endothelium to rapidly replace desquamating cells. Furthermore, these small areas of mechanical denudation do not stimulate smooth muscle proliferation. Finally, careful studies of hyperlipemic and hypertensive animals have failed to demonstrate any actual denudation.The possibility remains that denudation occurs repeatedly, with extremely brief periods of subendothelial exposure. Thus lesion formation could represent the cumulative record of multiple, tiny incidents. This hypothesis is, however, difficult to test. Less dramatic forms of injury which may be of interest include alterations of endothelial cell functions in replicating cells as well as alterations in function which may occur independent of any cell loss. This last category receives new emphasis today because of the rapid increase in the number of functions identified in endothelial cells. These include the apparent ability of endothelial cells to synthesize a growth factor which can stimulate smooth muscle proliferation in the absence of the platelet derived growth factor.This work was supported by NIH grants: HL-03174. HL-18645, HLC-7312 and a grant from the R.J. Reynolds Industries, Inc. Dr. Schwartz is an Established Investigator of the American Heart Association.