HDL-free cholesterol influx into macrophages and transfer to LDL correlate with HDL-free cholesterol content
High-density lipoprotein (HDL)-free cholesterol (FC) transfers to other lipoproteins and cells, the former by a spontaneous mechanism and the latter by both spontaneous and receptor-mediated mechanisms. Macrophages are an important cell type in all stages of atherosclerotic cardiovascular disease (A...
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| Language: | English |
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Elsevier
2025-01-01
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| Series: | Journal of Lipid Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227524002128 |
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| author | Dedipya Yelamanchili Baiba K. Gillard Antonio M. Gotto, Jr. Miguel Caínzos Achirica Khurram Nasir Alan T. Remaley Corina Rosales Henry J. Pownall |
| author_facet | Dedipya Yelamanchili Baiba K. Gillard Antonio M. Gotto, Jr. Miguel Caínzos Achirica Khurram Nasir Alan T. Remaley Corina Rosales Henry J. Pownall |
| author_sort | Dedipya Yelamanchili |
| collection | DOAJ |
| description | High-density lipoprotein (HDL)-free cholesterol (FC) transfers to other lipoproteins and cells, the former by a spontaneous mechanism and the latter by both spontaneous and receptor-mediated mechanisms. Macrophages are an important cell type in all stages of atherosclerotic cardiovascular disease (ASCVD), and the magnitude of FC efflux from macrophages to HDL, a metric of HDL function, inversely associated with several metrics of ASCVD. Very high plasma HDL concentrations are associated with increased all-cause and ASCVD mortality, suggesting that the reverse process, FC influx from HDL into macrophages, is atherogenic. We hypothesize that HDL-FC is a metric of dysfunctional HDL, and when combined with HDL particle number (HDL-P), is an ASCVD risk factor. The magnitude of FC influx from HDL to macrophages is expected to be a function of HDL-P and HDL-FC content. Here we show that plasma HDL-FC content varies 2-fold among normolipidemic human subjects and linearly correlates with low-density lipoprotein (LDL)-FC content. The influx of HDL-FC into macrophages and transfer to LDL increase linearly with HDL-FC. As expected, the influx of HDL-FC into macrophages and the transfer to LDL are positively correlated. These data support the hypothesis that high HDL FC content is a marker for dysfunctional HDL, resulting in greater influx into macrophages and greater HDL-FC transfer to LDL. HDL-FC transfer to LDL is a valid surrogate for influx into macrophages. This study of HDL composition and function of normolipidemic subjects provides the basis for further investigation and establishment of HDL-FC content as an ASCVD risk factor. |
| format | Article |
| id | doaj-art-6d7cba0aea5d4f68b28b03eccc94afe4 |
| institution | Kabale University |
| issn | 0022-2275 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj-art-6d7cba0aea5d4f68b28b03eccc94afe42025-01-30T05:12:37ZengElsevierJournal of Lipid Research0022-22752025-01-01661100707HDL-free cholesterol influx into macrophages and transfer to LDL correlate with HDL-free cholesterol contentDedipya Yelamanchili0Baiba K. Gillard1Antonio M. Gotto, Jr.2Miguel Caínzos Achirica3Khurram Nasir4Alan T. Remaley5Corina Rosales6Henry J. Pownall7Department of Medicine, Houston Methodist, Houston, TX, USADepartment of Medicine, Houston Methodist, Houston, TX, USA; Department of Medicine, Weill Cornell Medicine, New York, NY, USADepartment of Medicine, Houston Methodist, Houston, TX, USA; Department of Medicine, Weill Cornell Medicine, New York, NY, USAHospital del Mar Research Institute, Barcelona, SpainDepartment of Medicine, Weill Cornell Medicine, New York, NY, USA; Department of Cardiology and Houston Methodist DeBakey Heart & Vascular Center, Houston Methodist, Houston, TX, USALipoprotein Metabolism Laboratory, Translational Vascular Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USADepartment of Medicine, Houston Methodist, Houston, TX, USA; Department of Medicine, Weill Cornell Medicine, New York, NY, USADepartment of Medicine, Houston Methodist, Houston, TX, USA; Department of Medicine, Weill Cornell Medicine, New York, NY, USA; For correspondence: Henry J. PownallHigh-density lipoprotein (HDL)-free cholesterol (FC) transfers to other lipoproteins and cells, the former by a spontaneous mechanism and the latter by both spontaneous and receptor-mediated mechanisms. Macrophages are an important cell type in all stages of atherosclerotic cardiovascular disease (ASCVD), and the magnitude of FC efflux from macrophages to HDL, a metric of HDL function, inversely associated with several metrics of ASCVD. Very high plasma HDL concentrations are associated with increased all-cause and ASCVD mortality, suggesting that the reverse process, FC influx from HDL into macrophages, is atherogenic. We hypothesize that HDL-FC is a metric of dysfunctional HDL, and when combined with HDL particle number (HDL-P), is an ASCVD risk factor. The magnitude of FC influx from HDL to macrophages is expected to be a function of HDL-P and HDL-FC content. Here we show that plasma HDL-FC content varies 2-fold among normolipidemic human subjects and linearly correlates with low-density lipoprotein (LDL)-FC content. The influx of HDL-FC into macrophages and transfer to LDL increase linearly with HDL-FC. As expected, the influx of HDL-FC into macrophages and the transfer to LDL are positively correlated. These data support the hypothesis that high HDL FC content is a marker for dysfunctional HDL, resulting in greater influx into macrophages and greater HDL-FC transfer to LDL. HDL-FC transfer to LDL is a valid surrogate for influx into macrophages. This study of HDL composition and function of normolipidemic subjects provides the basis for further investigation and establishment of HDL-FC content as an ASCVD risk factor.http://www.sciencedirect.com/science/article/pii/S0022227524002128cholesterol/traffickingLDLLipoprotein/KineticsCholesterol/MetabolismLipidsHDL function |
| spellingShingle | Dedipya Yelamanchili Baiba K. Gillard Antonio M. Gotto, Jr. Miguel Caínzos Achirica Khurram Nasir Alan T. Remaley Corina Rosales Henry J. Pownall HDL-free cholesterol influx into macrophages and transfer to LDL correlate with HDL-free cholesterol content Journal of Lipid Research cholesterol/trafficking LDL Lipoprotein/Kinetics Cholesterol/Metabolism Lipids HDL function |
| title | HDL-free cholesterol influx into macrophages and transfer to LDL correlate with HDL-free cholesterol content |
| title_full | HDL-free cholesterol influx into macrophages and transfer to LDL correlate with HDL-free cholesterol content |
| title_fullStr | HDL-free cholesterol influx into macrophages and transfer to LDL correlate with HDL-free cholesterol content |
| title_full_unstemmed | HDL-free cholesterol influx into macrophages and transfer to LDL correlate with HDL-free cholesterol content |
| title_short | HDL-free cholesterol influx into macrophages and transfer to LDL correlate with HDL-free cholesterol content |
| title_sort | hdl free cholesterol influx into macrophages and transfer to ldl correlate with hdl free cholesterol content |
| topic | cholesterol/trafficking LDL Lipoprotein/Kinetics Cholesterol/Metabolism Lipids HDL function |
| url | http://www.sciencedirect.com/science/article/pii/S0022227524002128 |
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