Reverse Transport of Cholesterol Is the Reason for Resistance to Development of Atherosclerosis in Prague Hereditary Hypercholesterolemic (PHHC) Rat

Abstract

The Prague Hereditary Hypercholesterolemic (PHHC) rat is a model of hypercholesterolemia. In previous experiments, it was found to be completely resistant to the development of atherosclerosis. It was assumed that the reverse transport of cholesterol (RCT) might be the reason for this resistance. In this study, RCT was measured in vivo by cholesterol efflux from macrophages to plasma, using previously established methods for RCT in mice (Rader 2003), optimized for measurements in rats. Primary cell culture of macrophages was labeled with 14C-cholesterol and then injected intraperitoneally into rats. Plasma and feces were collected at 24 and 48 h. The plasma 14C-cholesterol levels at both 24 and 48 h were significantly higher in male PHHC rats compared to control Wistar rats. The PHHC rats excreted less 14C-cholesterol in feces in 24 and 48 h compared to Wistar rats. The largest pool of 14C-cholesterol was found in the adipose tissue of PHHC rats and in contrast lower levels of 14C-cholesterol were measured in the liver and muscle tissues of PHHC rats compared with Wistar rats. Increasing release of 14C-cholesterol efflux from macrophages demonstrates accelerated RTC and leads to prevention of atherogenesis in PHHC rats.