2023
DOI: 10.1161/atvbaha.122.317898
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Lp-PLA 2 (Lipoprotein-Associated Phospholipase A 2 ) Deficiency Lowers Cholesterol Levels and Protects Against Atherosclerosis in Rabbits

Abstract: Background: Elevated plasma Lp-PLA 2 (lipoprotein-associated phospholipase A 2 ) activity is closely associated with an increased risk of cardiovascular events. However, whether and how Lp-PLA 2 is directly involved in the pathogenesis of atherosclerosis is still unclear. To examine the hypothesis that Lp-PLA 2 could be a potential preventative target of atherosclerosis, we… Show more

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Cited by 7 publications
(3 citation statements)
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“…Lp-PLA2 downregulation showed the consistent anti-inflammatory effect in NASH with that in cardiovascular disease ( Sun et al, 2017 ). In accordance with our findings, a study by Chen et al (2023) demonstrated that Lp-PLA2 knockdown rabbits had reduced macrophages and inflammatory cytokine expression, and that macrophages of homozygous Lp-PLA2 knockout rabbits were insensitive to M1 polarization. In addition, the unbalance of lipid homeostasis in liver is an important pathological feature in NASH ( Ipsen, Lykkesfeldt & Tveden-Nyborg, 2018 ).…”
Section: Discussionsupporting
confidence: 92%
“…Lp-PLA2 downregulation showed the consistent anti-inflammatory effect in NASH with that in cardiovascular disease ( Sun et al, 2017 ). In accordance with our findings, a study by Chen et al (2023) demonstrated that Lp-PLA2 knockdown rabbits had reduced macrophages and inflammatory cytokine expression, and that macrophages of homozygous Lp-PLA2 knockout rabbits were insensitive to M1 polarization. In addition, the unbalance of lipid homeostasis in liver is an important pathological feature in NASH ( Ipsen, Lykkesfeldt & Tveden-Nyborg, 2018 ).…”
Section: Discussionsupporting
confidence: 92%
“…Within vascular intimal tissue, hydrolysis of Ox-LDL into oxidized fatty acids contribute to endothelial dysfunction, inflammation, and foam cell formation which may alter vascular architecture 39 . Progressive atherogenesis and vascular remodeling, reflected by persistent elevations in plasma TIMP-1 and TIMP-2 despite recovery 40 is likely to contribute to the increased thromboembolic events documented following acute severe COVID-19 which has drawn significant scientific interest 41 .…”
Section: Discussionmentioning
confidence: 99%
“…ApoE and LDL receptor ( LDLR ) knockout rabbit models created using CRISPR/Cas9 technology developed severe hyperlipidemia when exposed to a cholesterol-rich diet, showing importance for studying human hyperlipidemia and familial hypercholesterolemia ( Yang et al, 2014 ; Yuan et al, 2019 ). Most recently, Chen et al ( 2023 ) established a rabbit model deficient in the CVD risk factor lipoprotein-associated phospholipase A 2 ( Lp-PLA 2 ) and demonstrated that Lp-PLA 2 regulated blood lipid homeostasis, protecting against dietary cholesterol-induced atherosclerosis ( Chen et al, 2023 ). Overall, aided by genome editing, rabbits are expected to greatly promote investigations of CVD-related spontaneous hyperlipidemia and atherosclerosis.…”
Section: Generation Of Genome-edited Rabbits In Biomedical Researchmentioning
confidence: 99%