Effect of alterations of blood cholesterol levels on macrophages in the myocardium of New Zealand White rabbits

We investigated the effect of alterations of blood cholesterol levels on macrophages (m phi) in the myocardium of New Zealand White (NZW) rabbits, Three groups of NZW rabbits were used: controls, rabbits fed a 0.5% cholesterol-enriched diet (CH-D) for 96 days, and rabbits fed a 0.5% CH-D for 96 days followed by normal chow for 4 months, Immunohistochemical analysis by mAbs directed against m phi (RAM-11) and Mn superoxide dismutase (MnSOD) were quantified by computer-assisted morphometry. Using cultured human and rabbit m phi, a cross-reaction of the human MnSOD mAbs was found as well as the predominant localization of MnSOD-immunoreactivity (IR) in mitochondria. In group I, only a very few RAM-11-immunoreactive (ir) m phi occurred in the interstitial space of the myocardium, In group II blood cholesterol levels significantly increased Fn parallel with the numbers of m phi, which often contained lipid droplets (foam cells), Although blood cholesterol concentrations regressed about 10-fold in group III, m phi in the myocardium were found to be reduced only about 20%. Most m phi were also MnSOD-ir. In atherosclerotic coronary arteries RAM-11-IR was located in m phi and also extracellularly, whereas MnSOD-IR was found only in m phi. Drastically induced MnSOD in the mitochondria of m phi is suggested as an indicator of increased oxidative stress caused by in vitro conditions or by phagocytosis of low-density lipoprotein in vivo. Elevation of the cholesterol level leads to a long-term increase and its regression results in a delayed reduction of such m phi, which seem to play a key role in the atherogenesis of the coronary arteries as well.