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Enrichment of High-Density Lipoproteins with Phosphatidylethanolamine (36:5) Impairs Their Protective Biological Activities and is Associated with Atherosclerosis in Women

Atherosclerosis(2022)

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摘要
Background and Aims : Circulating concentrations of high-density lipoprotein-Cholesterol (HDL-C) are inversely associated to cardiovascular diseases (CVD) which reflect the atheroprotective activities of HDL. Phospholipidome of HDL is a major determinant of their activities and alterations of HDL phospholipidome and functions are common features of CVD patients. Plasma lipidome analyses reported that phosphatidylethanolamine (PE) (36:5) is associated with cardiovascular diseases. The objective of the present study was to determine if such association results in part from an impairment of the protective functions of HDL.Methods: Reconstituted HDL (rHDL) enriched with PE (36:5)Results: PE (36:5) rHDL exhibited a reduced capacity to promote cholesterol efflux from human THP-1 macrophages as compared to control rHDL. Moreover, the anti-inflammatory property of rHDL on the expression of some cytokines and chemokines was abolished upon enrichment of PE (36:5) in human THP-1 macrophages stimulated with LPS. Circulating PE (36:5) content of HDL2 isolated from 86 metabolically healthy women was significantly and positively correlated with carotid intima-media thickness in both univariate (β=0.359, p=0.0008) and multivariate (β=0.255, p=0.0116) regression analyses after adjustment for CVD risk factors. Moreover, unadjusted analyses revealed significant associations between the highest tertile (Ter3) of PE (36:5) in HDL2 and both the presence of atherosclerotic plaques in carotid arteries (OR : 3.93; 95%CI: 1.26-12.3, p = 0.0277 for Ter3 vs Ter1) and with coronary artery calcification score >100 (OR : 4.23; 95%CI: 1.16-15.4, p = 0.0379; Ter1 vs Ter3).Conclusions: Our study demonstrates that PE (36:5) content of HDL2 is a predictor of dysfunctional HDL and CVD in women. Background and Aims : Circulating concentrations of high-density lipoprotein-Cholesterol (HDL-C) are inversely associated to cardiovascular diseases (CVD) which reflect the atheroprotective activities of HDL. Phospholipidome of HDL is a major determinant of their activities and alterations of HDL phospholipidome and functions are common features of CVD patients. Plasma lipidome analyses reported that phosphatidylethanolamine (PE) (36:5) is associated with cardiovascular diseases. The objective of the present study was to determine if such association results in part from an impairment of the protective functions of HDL. Methods: Reconstituted HDL (rHDL) enriched with PE (36:5) Results: PE (36:5) rHDL exhibited a reduced capacity to promote cholesterol efflux from human THP-1 macrophages as compared to control rHDL. Moreover, the anti-inflammatory property of rHDL on the expression of some cytokines and chemokines was abolished upon enrichment of PE (36:5) in human THP-1 macrophages stimulated with LPS. Circulating PE (36:5) content of HDL2 isolated from 86 metabolically healthy women was significantly and positively correlated with carotid intima-media thickness in both univariate (β=0.359, p=0.0008) and multivariate (β=0.255, p=0.0116) regression analyses after adjustment for CVD risk factors. Moreover, unadjusted analyses revealed significant associations between the highest tertile (Ter3) of PE (36:5) in HDL2 and both the presence of atherosclerotic plaques in carotid arteries (OR : 3.93; 95%CI: 1.26-12.3, p = 0.0277 for Ter3 vs Ter1) and with coronary artery calcification score >100 (OR : 4.23; 95%CI: 1.16-15.4, p = 0.0379; Ter1 vs Ter3). Conclusions: Our study demonstrates that PE (36:5) content of HDL2 is a predictor of dysfunctional HDL and CVD in women.
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