Accumulation of lipoproteins containing apo B in the aorta of cholesterol-fed cynomolgus monkeys

Abstract

Accumulation of lipoproteins containing apo B in the aortic arch of cholesterol-fed cynomolgus monkeys was determined using an electroimmunoassay (EIA) to quantitate apo B. A loosely-bound fraction of apo B was measured by electrophoresing minces of whole wall thickness of aorta inserted directly into a gel containing antibodies to monkey normolipemic LDL. Normolipemic LDL was used as a standard. A tightly-bound apo B fraction was measured by digesting the once-electrophoresed minces with elastase and inserting the entire digest into wells of a second EIA using normolipemic LDL treated with elastase as a standard. These two fractions of apo B were determined in aortas of 7 animals fed an atherogenic diet for 24 months, 4 animals fed a control diet for 24 months, 4 animals fed an atherogenic diet for 30 months, and 2 animals fed a control chow for this time interval. The apo B values were compared to plasma cholesterol and HDL cholesterol concentrations. The extent and severity of atherosclerosis in the aortic arch was estimated by measuring the cross-sectioned intimal area of thoracic and abdominal aortas. The mean value of loosely-bound apo B, expressed either as ng protein per mg tissue wet weight or per mm 2 intimal surface area, was increased over controls for those animals fed the atherogenic diet for 24 months. Likewise tightly-bound apo B was increased for this time interval. Apo B values for both loosely- and tightly-bound fractions in animals fed the atherogenic diet for 30 months were higher than control values, and were also significantly higher than for those animals fed the atherogenic diet for 24 months. Loosely- and tightly-bound apo B values were evenly divided in both groups of hypercholesterolemic animals, whereas tightly-bound apo B was not found in any control animals. These results suggest that diet-induced hypercholesterolemia in cynomolgus monkeys results in accumulation of lipoproteins containing apo B (probably LDL) in the aorta in both loosely- and tightly-bound forms, and that total lipoprotein accumulation increases with further time on this diet, probably as a result of further development of atherosclerotic lesions.