Increased Hepatic Expression of Endothelial Lipase Inhibits Cholesterol Diet–Induced Hypercholesterolemia and Atherosclerosis in Transgenic Rabbits

Wang, Chuan; Nishijima, Ken‐ichi; Kitajima, Shuji; Niimi, Manabu; Yan, Hai‐Xing; Chen, Yajie; Niu, Bo; Matsuhisa, Fumikazu; Liu, Enqi; Zhang, Jifeng; Chen, Y. Eugene; Fan, Jianglin

doi:10.1161/atvbaha.117.309139

Cited by 33 publications

(34 citation statements)

References 31 publications

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“…In the rabbit model, HDL-C levels and atherosclerotic lesions were reduced by EL overexpression. 64 In the mouse model, HDL levels were similarly reduced, but reverse cholesterol transport was not dampened unless hepatic scavenger receptor class B type I was inhibited. 65 Furthermore, a Mendelian randomization study found that carriers of the LIPG 396Ser allele had higher HDL-C but similar levels of other lipid and non-lipid risk factors for MI compared with non-carriers; yet this allele was not associated with reduced risk of MI.…”

Section: High-density Lipoproteinmentioning

confidence: 97%

Highlighting Residual Atherosclerotic Cardiovascular Disease Risk

Matsuura

Kanter

Bornfeldt

2019

ATVB

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Section: High-density Lipoproteinmentioning

confidence: 97%

Highlighting Residual Atherosclerotic Cardiovascular Disease Risk

Matsuura

Kanter

Bornfeldt

2019

ATVB

View full text Add to dashboard Cite

“…Previous studies have shown that EL mediates HDL-cholesterol (HDL-C) levels along with VLDL levels [21, 26]. Recently, we found that expression of hepatic EL showed a significant influence on plasma lipids and lipoprotein metabolism [27]. Interestingly, increased hepatic expression of EL inhibits cholesterol diet–induced hypercholesterolemia and protects against atherosclerosis in male Tg rabbits but not in female Tg rabbits.…”

Section: Introductionmentioning

confidence: 98%

Sex hormones affect endothelial lipase-mediated lipid metabolism and atherosclerosis

et al. 2019

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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.

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“…In this study, rabbits at the age of 4 months were used unless otherwise specified. All rabbits were fed either with a chow diet or cholesterol‐rich diet containing 0.5% cholesterol and 3% soybean oil (see below) . The rabbits were allowed access to the diet and water ad libitum.…”

Section: Methodsmentioning

confidence: 99%

“…The aortas were en face stained by Sudan IV solution for quantitative analysis of the gross atherosclerotic lesion area as described previously . For microscopic quantification of the lesion area, each segment of the aorta arch from all rabbits was cut into cross sections as reported previously . Then, all specimens were embedded in paraffin and sections (3 μm) were stained with haematoxylin and eosin (HE) and elastica van Gieson (EVG).…”

Section: Methodsmentioning

confidence: 99%

Macrophage‐derived MMP‐9 enhances the progression of atherosclerotic lesions and vascular calcification in transgenic rabbits

Chen

Waqar

Nishijima

et al. 2020

J Cellular Molecular Medi

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Matrix metalloproteinase-9 (MMP-9), or gelatinase B, has been hypothesized to be involved in the progression of atherosclerosis. In the arterial wall, accumulated macrophages secrete considerable amounts of MMP-9 but its pathophysiological functions in atherosclerosis have not been fully elucidated. To examine the hypothesis that macrophage-derived MMP-9 may affect atherosclerosis, we created MMP-9 transgenic (Tg) rabbits to overexpress the rabbit MMP-9 gene under the control of the scavenger receptor A enhancer/promoter and examined their susceptibility to cholesterol diet-induced atherosclerosis. Tg rabbits along with non-Tg rabbits were fed a cholesterol diet for 16 and 28 weeks, and their aortic and coronary atherosclerosis was compared. Gross aortic lesion areas were significantly increased in female Tg rabbits at 28 weeks; however, pathological examination revealed that all the lesions of Tg rabbits fed a cholesterol diet for either 16 or 28 weeks were characterized by increased monocyte/macrophage accumulation and prominent lipid core formation compared with those of non-Tg rabbits. Macrophages isolated from Tg rabbits exhibited higher infiltrative activity towards a chemoattractant, MCP-1 in vitro and R E FE R E N C E S 1. Gross J, Lapiere CM. Collagenolytic activity in amphibian tissues: a tissue culture assay. Additional supporting information may be found online in the Supporting Information section. How to cite this article: Chen Y, Waqar AB, Nishijima K, et al. Macrophage-derived MMP-9 enhances the progression of atherosclerotic lesions and vascular calcification in transgenic rabbits. J Cell Mol Med. 2020;24:4261-4274. https://doi.

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Increased Hepatic Expression of Endothelial Lipase Inhibits Cholesterol Diet–Induced Hypercholesterolemia and Atherosclerosis in Transgenic Rabbits

Cited by 33 publications

References 31 publications

Highlighting Residual Atherosclerotic Cardiovascular Disease Risk

Highlighting Residual Atherosclerotic Cardiovascular Disease Risk

Sex hormones affect endothelial lipase-mediated lipid metabolism and atherosclerosis

Macrophage‐derived MMP‐9 enhances the progression of atherosclerotic lesions and vascular calcification in transgenic rabbits

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