Atherosclerosis in a rhesus monkey with genetic hypercholesterolemia and elevated plasma Lp(a).

ABSTRACT

A female rhesus monkey with a marked elevation of total plasma cholesterol LDL and Lp(a) while on a low-fat, low-cholesterol diet, died at 22 years of age. Her spontaneous hypercholesterolemia was related to a genetically determined LDL receptor deficiency (Scanu, A.M. et al., J. Lipid Res., 29 (1988) 1671). Autopsy revealed grossly visible multifocal to diffuse raised yellow plaques predominantly in the aorta and, to a lesser extent, in the coronary arteries. Microscopically, the plaques in the aorta and in the coronary arteries showed heavy lipid deposition. Some had features seen in advanced human atherosclerotic plaques, including a fibrous cap and a necrotic core. Immunohistochemical staining showed a co-localization of apo(a) with apo B in lesion sites, a pattern seen frequently in advanced human atherosclerotic plaques. Evidence of fibrinogen/fibrin in the plaque areas was also seen, but was not co-localised with either Lp(a) or apo B. This monkey developed progressive atherosclerosis which was not induced by diet, but rather was dependent on the LDL receptor deficiency with a possible contribution by the elevated plasma levels of Lp(a).