Hypercholesterolemia-Induced Long-Term Increase of Macrophages in the Myocardium of New Zealand White Rabbits

The effect of hypercholesterolemia on the number, immunological phenotype and oxidative stress-dependent processes of macrophages (MΦ) and dendritic cells (DC) was studied in New Zealand White rabbits. The left ventricular myocardium was immunohistochemically analyzed in group I (control), which was on standard chow, and groups II and III, which both received a 0.5% cholesterol-enriched diet for 96 days, but thereafter, only group III was fed standard chow for 4 months. In the myocardial interstitium of group I, (1) significantly less RAM-11-immunoreactive (ir) MΦ than S-100-ir DC were found; (2) both, MΦ and DC, were similar major histocompatibility complex (MHC) class II molecules LN3-, ISCR3-, and 2.06-ir; (3) all MΦ and most DC were manganese superoxide dismutase (MnSOD)-ir and homing receptor CD44-ir. In group II, only MΦ increased about 10-fold in the myocardium in parallel to the about 40-fold increase of the serum cholesterol levels. In group III, the elevated serum cholesterol levels significantly decreased (about 90%), while the MΦ still remained significantly increased (about 8-fold). The cellular immunoreactivities of MHC class II molecules, as well as MnSOD and CD44 did not change in groups II and III in comparison to group I. We suggest that mainly the MΦ, which increase within the myocardium of rabbits after elevation of serum cholesterol levels and remain significantly increased for a long time after decrease of the blood lipid levels, might initiate or aggravate eventual complications such as coronary atherosclerosis and myocardial fibrosis.