J. Morgan et al., OXIDATION OF LOW-DENSITY-LIPOPROTEIN BY BOVINE AND PORCINE AORTIC ENDOTHELIAL-CELLS AND PORCINE ENDOCARDIAL CELLS IN CULTURE, Atherosclerosis, 102(2), 1993, pp. 209-216
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 e
ndothelial cells (both in primary culture and in subcultures) were cap
able of consistently modifying LDL, increasing its uptake and degradat
ion 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 consist
ently modified LDL in 24 h. The modification of LDL by bovine aortic e
ndothelial cells was an oxidative process, as the chain-breaking antio
xidants, alpha-tocopherol and probucol, completely or greatly inhibite
d it. Thus, bovine aortic endothelial cells are capable of oxidising L
DL but they are slower at doing so than are certain other types of cel
ls. Nitric oxide generated by activated macrophages has very recently
been shown to inhibit their oxidation of LDL. We have therefore invest
igated 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 ef
fect on LDL oxidation, however, suggesting that the basal release of n
itric oxide by these cells was insufficient to inhibit their oxidation
of LDL. We also report that porcine right ventricular endocardial cel
ls and aortic endothelial cells can oxidatively modify LDL over 24 h t
o greatly increase its degradation by macrophages (up to about 6-fold
and 9-fold greater than control LDL, respectively).