Cellular proliferation in atherosclerosis and hypertension.
We have tried to compare the proliferative responses seen in two vascular diseases: atherosclerosis and hypertension. Both diseases involve endothelial injury and proliferation, but our knowledge of this phenomenon is just beginning to emerge. In atherosclerosis the best evidence is that denudation does not occur in the normal young animal. Man, however, ages over a much longer time than our usual animal models, and the study of denudation during the chronic progression of atherosclerotic lesions remains to be done. We need to consider the possibility that repetitive, small lesions may occur at sites of endothelial turnover. We also need to know more about the possible role of nondenuding injuries, including death of endothelial cells in situ and the apparent increased stickiness of endothelial cells and monocytes during the early stages of hypercholesterolemia. The role of endothelial injury in hypertension also needs more study. We know that extensive denudation and thrombosis occur in small vessels subjected to high blood pressure. It is highly probable that release of PDGF occurs at these sites, possibly accounting for the characteristic hyperplasia seen in malignant hypertension. Whether this process is related to the more subtle changes in vessel wall mass seen in chronic hypertension remains unknown. Finally, there are remarkable differences in the proliferative behavior of the smooth muscle cells themselves in these two diseases. Hypertensive vascular disease is, in large part, a disease of the media. Atherosclerosis is characterized by intimal hyperplasia. Injury results in migration of smooth muscle cells from the media and cell division in the intima. It is possible to identify chemotactic factors using putative atherosclerosis risk factors or normal components of serum. This has already been done for one component of lesion formation, PDGF, and there is a report of a monocyte chemotactic factor released by smooth muscle cells. Factors released by other components of lesions may be of considerable interest. In contrast, changes in hypertension occur within a more orderly preservation of vessel wall structure. The wall thickens, but this occurs by increased synthesis of cell mass in the media. The cells themselves do not even divide, but they undergo a form of amitotic replication of their DNA.(ABSTRACT TRUNCATED AT 400 WORDS)
D000818:Animals; D001161:Arteriosclerosis / Q000378:metabolism / Q000473:pathology*; D001792:Blood Platelets / Q000378:metabolism / Q000473:pathology; D002455:Cell Division; D004247:DNA / Q000378:metabolism; D004727:Endothelium / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D006937:Hypercholesterolemia / Q000378:metabolism / Q000473:pathology; D006973:Hypertension / Q000378:metabolism / Q000473:pathology*; D008938:Mitosis; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D013927:Thrombosis / Q000378:metabolism / Q000473:pathology
D010982:Platelet-Derived Growth Factor; D004247:DNA