Arterial Injury Alters Metabolism Of The Arterial Wall

Abstract

Results of our previous experiments indicate that following de-endothelialization aortic intima was thicker and contained more lipid in re-endothelialized (RA) and not de-en- dothelialized areas (DA) as we anticipated. Chemical analysis revealed that, in rabbits fed lipid-poor diets, there was 2 to 3 times as much cholesteryl ester (CE) in RA as compared to DA or uninjured aortas. In hypercholesterole- mic rabbits, aortic total cholesterol content correlated with serum cholesterol concentration in RA but not DA.Taken together, these findings suggest that aortic cholesterol (CH) and CE accumulation are not simply a result of increased filtration of lipoproteins into the de-endo- thelialized aorta but may result from altered metabolism of the arterial wall. Previous findings showing increased glycosaminoglycan (GAG) accumulation in RA supported this concept of altered metabolism and suggest that these GAGs may sequester lipoproteins. Recent experiments indicate that: 1) CE synthetic and hydrolytic activity as well as activities of several marker enzymes were increased in injured aortas, 2) CE hydrolytic activity was relatively greater in DA as compared to RA, 3) Neointimal smooth muscle cells (SMC) in DA synthesized increased quantities of PGI2 and that PGI2 increased CE hydrolase activity of SMC and 4) RA accumulate more 125I-apo-B-lipoproteins than adjacent DA. In conclusion, results indicate that RA accumulate more CE rich apo-B-lipoproteins and have decreased ability to degrade CE. This may, at least in part, account for the increased CH and CE accumulation in RA. Further, the findings suggest that arterial injury alters arterial wall metabolism and that interactions between neointimal smooth muscle cells and endothelial cells may modify these metabolic changes.