Gender differences in response to a hypercholesterolemic diet in hamsters: effects on plasma lipoprotein cholesterol concentrations and early aortic atherosclerosis

Gender is a strong predictor of coronary heart disease (CHD) susceptibility and reports indicate that males are more likely to develop CHD compared to age-matched premenopausal females. To test whether similar gender differences exist in hamsters, 16 male and 16 female F1B Golden Syrian hamsters, aged 10 weeks, were fed a hypercholesterolemic nonpurified diet (HCD) containing 10% coconut oil and 0.05% cholesterol for 12 weeks. Plasma lipid and lipoprotein cholesterol concentrations, LDL oxidative susceptibility, LDL tocopherol concentrations, LDL fatty acid composition, LDL particle size, plasma estradiol and testosterone concentrations, and early aortic atherosclerosis were analyzed. Female hamsters had significantly lower plasma total cholesterol and nonhigh-density lipoprotein cholesterol (nonHDL-C) and greater high-density lipoprotein cholesterol (HDL-C) concentrations compared to male hamsters (−15, −33, and 33%; respectively). Female hamsters had significantly greater LDL particle size (4%), LDL 22:6 (21%) fatty acid, and rate of LDL oxidation (34%) compared to male hamsters. Female hamsters had a significantly higher concentration of plasma estradiol (49%) compared to male hamsters. Female hamsters also had significantly less early aortic atherosclerosis compared to male hamsters (−77%). In female hamsters, aortic fatty streak formation was significantly associated with plasma nonHDL-C (r=0.76, P<0.0007), LDL particle size (r=−0.66, P<0.005), plasma TC (r=0.68, P<0.004), and lag phase of LDL oxidation (r=0.84, P<0.02). In male hamsters, aortic fatty streak formation was significantly associated with plasma nonHDL-C (r=0.52, P<0.04), plasma TC (r=0.55, P<0.03), plasma TG (r=0.79, P<0.0003), and LDL 22:6 (r=−0.78, P<0.03) with no association with any measures of LDL oxidation susceptiblity. This study demonstrates that female hamsters have an improved plasma lipoprotein cholesterol profile, larger LDL particle size, and less early aortic atherosclerosis compared to male hamsters fed the same HCD.