Oxidation of low density lipoprotein by bovine and porcine aortic endothelial cells and porcine endocardial cells in culture

Abstract

Oxidation of low density lipoprotein (LDL) in atherosclerotic lesions may be involved in converting macrophages into cholesterol-laden foam cells, a major characteristic of atherosclerotic lesions. It has been reported, and is widely believed, that endothelial cells derived from rabbit, pig and human aortas, but not those derived from bovine aortas, are capable of oxidising LDL in vitro. We have re-investigated this subject and found that during a 48-h incubation period bovine aortic endothelial cells (both in primary culture and in subcultures) were capable of consistently modifying LDL, increasing its uptake and degradation by macrophages by more than 4-fold. Incubation of LDL with bovine aortic endothelial cells for only 24 h, however, produced inconsistent modification of the LDL, whereas mouse peritoneal macrophages consistently modified LDL in 24 h. The modification of LDL by bovine aortic endothelial cells was an oxidative process, as the chain-breaking antioxidants, α-tocopherol and probucol, completely or greatly inhibited it. Thus, bovine aortic endothelial cells are capable of oxidising LDL but they are slower at doing so than are certain other types of cells. Nitric oxide generated by activated macrophages has very recently been shown to inhibit their oxidation of LDL. We have therefore investigated whether or not the inhibition of the constitutive nitric oxide synthase of bovine or porcine aortic endothelial cells would increase their rate of oxidation of LDL. The inhibition of the enzyme had no effect on LDL oxidation, however, suggesting that the basal release of nitric oxide by these cells was insufficient to inhibit their oxidation of LDL. We also report that porcine right ventricular endocardial cells and aortic endothelial cells can oxidatively modify LDL over 24 h to greatly increase its degradation by macrophages (up to about 6-fold and 9-fold greater than control LDL, respectively).