Regional differences in arterial low density lipoprotein metabolism in surgically postmenopausal cynomolgus monkeys. Effects of estrogen and progesterone replacement therapy

Abstract

To determine if arterial lipoprotein metabolism may be involved in mediating well-known anatomic regional differences in susceptibility to atherosclerosis, arterial low density lipoprotein (LDL) metabolism and extent of atherosclerosis were studied in 17 ovariectomized female cynomolgus monkeys. The animals were fed an atherogenic diet for 18 weeks, during which time one group received 17 beta-estradiol and cyclic progesterone treatment (n = 9) and the controls received no hormone replacement therapy (n = 8). As reported previously, hormone replacement markedly reduced the accumulation of LDL in coronary arteries without affecting plasma lipoprotein patterns. We report here that LDL metabolism differed among arterial sites. LDL accumulation, LDL degradation rate, and the concentration of undegraded LDL were greatest in the coronary arteries and carotid bifurcations compared with the aorta, iliac arteries, and cerebral arteries. Although hormone replacement decreased indexes of LDL metabolism, there was no effect on intimal thickness or indexes of endothelial injury, such as leukocyte adhesion and endothelial cell turnover rate. There were, however, regional differences in these morphological parameters. The intima was thickest in the aorta, and leukocyte adhesion and endothelial cell turnover rates were greatest in the carotid bifurcation and thoracic aorta. The decreased accumulation and metabolism of LDL caused by hormone replacement therapy was specific to the arterial system and did not occur in the liver or other peripheral tissues.