$The Potential Role of Electronegative High-Density Lipoprotein H5 Subfraction in RA-Related Atherosclerosis$
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The Potential Role of Electronegative High-Density Lipoprotein H5 Subfraction in RA-Related Atherosclerosis

Although the heterogeneity of high-density lipoprotein-cholesterol (HDL-c) composition is associated with atherosclerotic cardiovascular risk, the link between electronegative subfractions of HDL-c and atherosclerosis in rheumatoid arthritis (RA) remains unknown. We examined the association of the p...

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Autores principales:	Ching-Kun Chang, Wei-Chung Cheng, Wen-Lung Ma, Po-Ku Chen, Chu-Huang Chen, Pei-Chun Shen, Chia-Ching Chen, Shih-Hsin Chang, Yi-Hua Lai, Der-Yuan Chen
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	high-density lipoprotein (HDL) electronegative subfractions of HDL H5 liquid chromatography/mass spectrometry (LC/MS) lipoprotein a (Lp(a)) atherosclerosis Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/28884091686b481ba7658ffe5911d500
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spelling	oai:doaj.org-article:28884091686b481ba7658ffe5911d5002021-11-11T16:53:32ZThe Potential Role of Electronegative High-Density Lipoprotein H5 Subfraction in RA-Related Atherosclerosis10.3390/ijms2221114191422-00671661-6596https://doaj.org/article/28884091686b481ba7658ffe5911d5002021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11419https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Although the heterogeneity of high-density lipoprotein-cholesterol (HDL-c) composition is associated with atherosclerotic cardiovascular risk, the link between electronegative subfractions of HDL-c and atherosclerosis in rheumatoid arthritis (RA) remains unknown. We examined the association of the percentage of the most electronegative subfraction of HDL-c (H5%) and RA-related atherosclerosis. Using anion-exchange purification/fast-protein liquid chromatography, we demonstrated significantly higher H5% in patients (median, 7.2%) than HC (2.8%, <i>p</i> < 0.005). Multivariable regression analysis revealed H5% as a significant predictor for subclinical atherosclerosis. We subsequently explored atherogenic role of H5 using cell-based assay. The results showed significantly higher levels of IL-1β and IL-8 mRNA in H5-treated (mean ± SD, 4.45 ± 1.22 folds, 6.02 ± 1.43-folds, respectively) than H1-treated monocytes (0.89 ± 0.18-folds, 1.03 ± 0.26-folds, respectively, both <i>p</i> < 0.001). In macrophages, H5 upregulated the mRNA and protein expression of IL-1β and IL-8 in a dose-dependent manner, and their expression levels were significantly higher than H1-treated macrophages (all <i>p</i> < 0.001). H5 induced more foam cell formation compared with H1-treated macrophages (<i>p</i> < 0.005). In addition, H5 has significantly lower cholesterol efflux capacity than H1 (<i>p</i> < 0.005). The results of nanoLC-MS/MS approach reveal that the best discriminator between high-H5% and normal-H5% is Apo(a), the main constituent of Lp(a). Moreover, Lp(a) level is a significant predictor for high-H5%. These observations suggest that H5 is involved in RA-related atherosclerosis.Ching-Kun ChangWei-Chung ChengWen-Lung MaPo-Ku ChenChu-Huang ChenPei-Chun ShenChia-Ching ChenShih-Hsin ChangYi-Hua LaiDer-Yuan ChenMDPI AGarticlehigh-density lipoprotein (HDL)electronegative subfractions of HDLH5liquid chromatography/mass spectrometry (LC/MS)lipoprotein a (Lp(a))atherosclerosisBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11419, p 11419 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	high-density lipoprotein (HDL) electronegative subfractions of HDL H5 liquid chromatography/mass spectrometry (LC/MS) lipoprotein a (Lp(a)) atherosclerosis Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	high-density lipoprotein (HDL) electronegative subfractions of HDL H5 liquid chromatography/mass spectrometry (LC/MS) lipoprotein a (Lp(a)) atherosclerosis Biology (General) QH301-705.5 Chemistry QD1-999 Ching-Kun Chang Wei-Chung Cheng Wen-Lung Ma Po-Ku Chen Chu-Huang Chen Pei-Chun Shen Chia-Ching Chen Shih-Hsin Chang Yi-Hua Lai Der-Yuan Chen The Potential Role of Electronegative High-Density Lipoprotein H5 Subfraction in RA-Related Atherosclerosis
description	Although the heterogeneity of high-density lipoprotein-cholesterol (HDL-c) composition is associated with atherosclerotic cardiovascular risk, the link between electronegative subfractions of HDL-c and atherosclerosis in rheumatoid arthritis (RA) remains unknown. We examined the association of the percentage of the most electronegative subfraction of HDL-c (H5%) and RA-related atherosclerosis. Using anion-exchange purification/fast-protein liquid chromatography, we demonstrated significantly higher H5% in patients (median, 7.2%) than HC (2.8%, <i>p</i> < 0.005). Multivariable regression analysis revealed H5% as a significant predictor for subclinical atherosclerosis. We subsequently explored atherogenic role of H5 using cell-based assay. The results showed significantly higher levels of IL-1β and IL-8 mRNA in H5-treated (mean ± SD, 4.45 ± 1.22 folds, 6.02 ± 1.43-folds, respectively) than H1-treated monocytes (0.89 ± 0.18-folds, 1.03 ± 0.26-folds, respectively, both <i>p</i> < 0.001). In macrophages, H5 upregulated the mRNA and protein expression of IL-1β and IL-8 in a dose-dependent manner, and their expression levels were significantly higher than H1-treated macrophages (all <i>p</i> < 0.001). H5 induced more foam cell formation compared with H1-treated macrophages (<i>p</i> < 0.005). In addition, H5 has significantly lower cholesterol efflux capacity than H1 (<i>p</i> < 0.005). The results of nanoLC-MS/MS approach reveal that the best discriminator between high-H5% and normal-H5% is Apo(a), the main constituent of Lp(a). Moreover, Lp(a) level is a significant predictor for high-H5%. These observations suggest that H5 is involved in RA-related atherosclerosis.
format	article
author	Ching-Kun Chang Wei-Chung Cheng Wen-Lung Ma Po-Ku Chen Chu-Huang Chen Pei-Chun Shen Chia-Ching Chen Shih-Hsin Chang Yi-Hua Lai Der-Yuan Chen
author_facet	Ching-Kun Chang Wei-Chung Cheng Wen-Lung Ma Po-Ku Chen Chu-Huang Chen Pei-Chun Shen Chia-Ching Chen Shih-Hsin Chang Yi-Hua Lai Der-Yuan Chen
author_sort	Ching-Kun Chang
title	The Potential Role of Electronegative High-Density Lipoprotein H5 Subfraction in RA-Related Atherosclerosis
title_short	The Potential Role of Electronegative High-Density Lipoprotein H5 Subfraction in RA-Related Atherosclerosis
title_full	The Potential Role of Electronegative High-Density Lipoprotein H5 Subfraction in RA-Related Atherosclerosis
title_fullStr	The Potential Role of Electronegative High-Density Lipoprotein H5 Subfraction in RA-Related Atherosclerosis
title_full_unstemmed	The Potential Role of Electronegative High-Density Lipoprotein H5 Subfraction in RA-Related Atherosclerosis
title_sort	potential role of electronegative high-density lipoprotein h5 subfraction in ra-related atherosclerosis
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/28884091686b481ba7658ffe5911d500
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The Potential Role of Electronegative High-Density Lipoprotein H5 Subfraction in RA-Related Atherosclerosis

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