The effect of intravenously injected beta very low density lipoprotein on small and large arterial injuries

A series of daily injections of beta very low density lipoprotein (beta-VLDL) was administered over 4-5 days to rabbits whose arteries contained either experimental circumferential lesions or areas of intimal thickening. The circumferential lesions were similar to those that occur spontaneously and were produced by the application of longitudinal tension. The intimal thickening was produced by denuding the endothelium with a balloon catheter. Over the period of injection of beta-VLDL the plasma cholesterol levels rose in a pulse-like manner from 60 to 100 mg/dl. Following cessation of injections the cholesterol levels initially rose further and then decreased to normal levels within 4 weeks. Injections of beta-VLDL, commencing 1-2 days after production of the circumferential lesions, resulted in an increase in the number of mononuclear leukocytes (primarily macrophages) and in a moderate accumulation of lipid by these cells and the medial smooth muscle cells. If the injections were started 14 days postinjury there was some accumulation of lipid in the large lesions but none in small lesions. There was no lipid accumulation in any lesions if the beta-VLDL was administered 3 months postinjury or if the animals were injected 2 days after injury and examined 3 months later. A very slight accumulation of lipid occurred in the intimal thickening, or neo-intima, following a series of beta-VLDL injections given to rabbits 2 or 6 weeks after balloon catheter injury. The series of injections produced a significant increase in the number of mononuclear leukocyte profiles per area of the neo-intima, suggesting an increased infiltration of these cells into the injured artery. These results suggest that a small transient increase in the plasma concentration of cholesterol-carrying lipoproteins may lead to increased infiltration of mononuclear leukocytes into areas of intimal thickening or areas of "spontaneously occurring" injury.