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) ra bbits, 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, Immunohisto chemical analysis by mAbs directed against m phi (RAM-11) and Mn super oxide dismutase (MnSOD) were quantified by computer-assisted morphomet ry. Using cultured human and rabbit m phi, a cross-reaction of the hum an MnSOD mAbs was found as well as the predominant localization of MnS OD-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 in creased Fn parallel with the numbers of m phi, which often contained l ipid droplets (foam cells), Although blood cholesterol concentrations regressed about 10-fold in group III, m phi in the myocardium were fou nd to be reduced only about 20%. Most m phi were also MnSOD-ir. In ath erosclerotic coronary arteries RAM-11-IR was located in m phi and also extracellularly, whereas MnSOD-IR was found only in m phi. Drasticall y induced MnSOD in the mitochondria of m phi is suggested as an indica tor of increased oxidative stress caused by in vitro conditions or by phagocytosis of low-density lipoprotein in vivo. Elevation of the chol esterol 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 i n the atherogenesis of the coronary arteries as well.