Key result
Increased hepatic expression of endothelial lipase reduced aortic atherosclerotic lesions by 61% in male transgenic rabbits, but this atheroprotective effect was completely eliminated after orchiectomy.
Why the study?
Gender differences in transgenic rabbits with increased hepatic expression of endothelial lipase suggested sex hormones may mediate endothelial lipase functions, influencing lipoprotein metabolism.
Effect estimate: 61% reduction
p-value: p=<0.05
The atheroprotective and lipid-lowering benefits of increased endothelial lipase expression are dependent on the presence of androgenic hormones in a rabbit model.
Hormonal mediation of EL lipid effects suggested by rabbit gender differences; leaves open translation to human dyslipidemia.
BACKGROUND: Endothelial lipase (EL) plays an important role in lipoprotein metabolism and atherosclerosis. To study the functional roles of EL, we recently generated transgenic (Tg) rabbits and reported that increased hepatic expression of EL in male Tg rabbits significantly reduced diet-induced hypercholesterolemia compared with non-Tg controls. This gender difference suggests that sex hormones may mediate EL functions thereby influencing lipoprotein metabolism. To examine this hypothesis, we compared the effects of orchiectomy and ovariectomy on plasma lipids and diet-induced atherosclerosis in both Tg and non-Tg rabbits. METHODS: Male rabbits were under orchiectomy whereas female rabbits were under ovariectomy. We compared plasma lipids, lipoproteins, and apolipoproteins of rabbits before and after surgery in each group fed either a chow diet or cholesterol-rich diet. RESULTS: On a chow diet, both male and female Tg rabbits showed lower plasma lipids than non-Tg counterparts and this lipid-lowering effect of EL was not affected by either orchiectomy in male or ovariectomy in female Tg rabbits. On a cholesterol diet; however, male Tg rabbits but not female Tg rabbits showed significant resistance to diet-induced hypercholesterolemia and atherosclerosis. The EL-mediated atheroprotective effect was eliminated after orchiectomy in male Tg rabbits. Female Tg rabbits showed similar levels of total cholesterol and lesion size of atherosclerosis compared with non-Tg rabbits and ovariectomy did not affect diet-induced hypercholesterolemia or atherosclerosis. CONCLUSION: These results suggest that increased EL protects against diet-induced hypercholesterolemia and atherosclerosis. The beneficial effect of EL was dependent upon the presence of androgenic hormones.
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Wang et al. (2019) studied Hypercholesterolemia and atherosclerosis (n=34). Endothelial lipase overexpression and castration (orchiectomy/ovariectomy) vs. Non-transgenic rabbits and uncastrated controls was evaluated on Aortic atherosclerotic lesion size (61% reduction, p=<0.05). Increased hepatic expression of endothelial lipase reduced aortic atherosclerotic lesions by 61% in male transgenic rabbits, but this atheroprotective effect was completely eliminated after orchiectomy.
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