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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| Language: | English |
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MDPI AG
2021-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/21/11419 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T06:02:26Z |
| format | Article |
| id | doaj.art-28884091686b481ba7658ffe5911d500 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T06:02:26Z |
| publishDate | 2021-10-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-28884091686b481ba7658ffe5911d5002023-11-22T20:51:53ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-10-0122211141910.3390/ijms222111419The Potential Role of Electronegative High-Density Lipoprotein H5 Subfraction in RA-Related AtherosclerosisChing-Kun Chang0Wei-Chung Cheng1Wen-Lung Ma2Po-Ku Chen3Chu-Huang Chen4Pei-Chun Shen5Chia-Ching Chen6Shih-Hsin Chang7Yi-Hua Lai8Der-Yuan Chen9Rheumatology and Immunology Center, China Medical University Hospital, Taichung 404, TaiwanThe Ph.D. Program for Cancer Biology and Drug Discovery, China Medical University and Academia Sinica, Taichung 404, TaiwanGraduate Institute of Biomedical Sciences, China Medical University, Taichung 404, TaiwanRheumatology and Immunology Center, China Medical University Hospital, Taichung 404, TaiwanVascular and Medicinal Research, Texas Heart Institute, Houston, TX 6770, USAResearch Center for Cancer Biology, China Medical University, Taichung 404, TaiwanSchool of Medicine, Chang Gung University, Tao-Yuan 333, TaiwanRheumatology and Immunology Center, China Medical University Hospital, Taichung 404, TaiwanRheumatology and Immunology Center, China Medical University Hospital, Taichung 404, TaiwanRheumatology and Immunology Center, China Medical University Hospital, Taichung 404, TaiwanAlthough 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.https://www.mdpi.com/1422-0067/22/21/11419high-density lipoprotein (HDL)electronegative subfractions of HDLH5liquid chromatography/mass spectrometry (LC/MS)lipoprotein a (Lp(a))atherosclerosis |
| spellingShingle | 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 International Journal of Molecular Sciences high-density lipoprotein (HDL) electronegative subfractions of HDL H5 liquid chromatography/mass spectrometry (LC/MS) lipoprotein a (Lp(a)) atherosclerosis |
| title | 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_short | 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 |
| topic | high-density lipoprotein (HDL) electronegative subfractions of HDL H5 liquid chromatography/mass spectrometry (LC/MS) lipoprotein a (Lp(a)) atherosclerosis |
| url | https://www.mdpi.com/1422-0067/22/21/11419 |
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