Sex hormones affect endothelial lipase-mediated lipid metabolism and atherosclerosis

Chuan Wang,Jianglin Fan,Fumikazu Matsuhisa,Shuji Kitajima,Manabu Niimi,Sijun Dong,Haizhao Yan,Jingyan Liang

doi:10.1186/s12944-019-1175-4

Abstract

BackgroundEndothelial 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.MethodsMale 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.ResultsOn 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.ConclusionThese 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.

Highlights

Atherosclerotic complications such as myocardial infarction and stroke are the major cause of morbidity and mortality in the world [1, 2]
Our current study showed that gender differences in lipid metabolism and atherosclerosis observed in Endothelial lipase (EL) Tg rabbits are dependent on the presence of androgens but not estrogens
Plasma lipids and lipoproteins On a chow diet, both male and female Tg rabbits showed significant reduction of plasma total cholesterol mainly caused by significant decrease of high-density lipoproteins (HDL)-C levels (Fig. 1)

Summary

Introduction

Atherosclerotic complications such as myocardial infarction and stroke are the major cause of morbidity and mortality in the world [1, 2]. Increased hepatic expression of EL inhibits cholesterol diet–induced hypercholesterolemia and protects against atherosclerosis in male Tg rabbits but not in female Tg rabbits This finding prompted us to envision that there is an interaction between EL and sex hormones thereby influencing 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. We compared the effects of orchiectomy and ovariectomy on plasma lipids and diet-induced atherosclerosis in both Tg and non-Tg rabbits

Methods

Results

Discussion

Conclusion