Aggregation and fusion of low-density lipoproteins in vivo and in vitro
Low-density lipoproteins (LDLs, also known as ‘bad cholesterol’) are the major carriers of circulating cholesterol and the main causative risk factor of atherosclerosis. Plasma LDLs are 20- to 25-nm nanoparticles containing a core of cholesterol esters surrounded by a phospholipid monolayer and a si...
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| Format: | Article |
| Language: | English |
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De Gruyter
2013-10-01
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| Series: | Biomolecular Concepts |
| Subjects: | |
| Online Access: | https://doi.org/10.1515/bmc-2013-0016 |
| _version_ | 1818730300076720128 |
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| author | Lu Mengxiao Gursky Olga |
| author_facet | Lu Mengxiao Gursky Olga |
| author_sort | Lu Mengxiao |
| collection | DOAJ |
| description | Low-density lipoproteins (LDLs, also known as ‘bad cholesterol’) are the major carriers of circulating cholesterol and the main causative risk factor of atherosclerosis. Plasma LDLs are 20- to 25-nm nanoparticles containing a core of cholesterol esters surrounded by a phospholipid monolayer and a single copy of apolipoprotein B (550 kDa). An early sign of atherosclerosis is the accumulation of LDL-derived lipid droplets in the arterial wall. According to the widely accepted ‘response-to-retention hypothesis’, LDL binding to the extracellular matrix proteoglycans in the arterial intima induces hydrolytic and oxidative modifications that promote LDL aggregation and fusion. This enhances LDL uptake by the arterial macrophages and triggers a cascade of pathogenic responses that culminate in the development of atherosclerotic lesions. Hence, LDL aggregation, fusion, and lipid droplet formation are important early steps in atherogenesis. In vitro, a variety of enzymatic and nonenzymatic modifications of LDL can induce these reactions and thereby provide useful models for their detailed analysis. Here, we summarize current knowledge of the in vivo and in vitro modifications of LDLs leading to their aggregation, fusion, and lipid droplet formation; outline the techniques used to study these reactions; and propose a molecular mechanism that underlies these pro-atherogenic processes. Such knowledge is essential in identifying endogenous and exogenous factors that can promote or prevent LDL aggregation and fusion in vivo and to help establish new potential therapeutic targets to decelerate or even block these pathogenic reactions. |
| first_indexed | 2024-12-17T22:59:35Z |
| format | Article |
| id | doaj.art-134111e13a234ce3ba11808a1b1000f3 |
| institution | Directory Open Access Journal |
| issn | 1868-5021 1868-503X |
| language | English |
| last_indexed | 2024-12-17T22:59:35Z |
| publishDate | 2013-10-01 |
| publisher | De Gruyter |
| record_format | Article |
| series | Biomolecular Concepts |
| spelling | doaj.art-134111e13a234ce3ba11808a1b1000f32022-12-21T21:29:27ZengDe GruyterBiomolecular Concepts1868-50211868-503X2013-10-014550151810.1515/bmc-2013-0016Aggregation and fusion of low-density lipoproteins in vivo and in vitroLu Mengxiao0Gursky Olga1Department of Physiology and Biophysics, Boston University School of Medicine, W321, 700 Albany Street, Boston, MA 02118, USADepartment of Physiology and Biophysics, Boston University School of Medicine, W321, 700 Albany Street, Boston, MA 02118, USALow-density lipoproteins (LDLs, also known as ‘bad cholesterol’) are the major carriers of circulating cholesterol and the main causative risk factor of atherosclerosis. Plasma LDLs are 20- to 25-nm nanoparticles containing a core of cholesterol esters surrounded by a phospholipid monolayer and a single copy of apolipoprotein B (550 kDa). An early sign of atherosclerosis is the accumulation of LDL-derived lipid droplets in the arterial wall. According to the widely accepted ‘response-to-retention hypothesis’, LDL binding to the extracellular matrix proteoglycans in the arterial intima induces hydrolytic and oxidative modifications that promote LDL aggregation and fusion. This enhances LDL uptake by the arterial macrophages and triggers a cascade of pathogenic responses that culminate in the development of atherosclerotic lesions. Hence, LDL aggregation, fusion, and lipid droplet formation are important early steps in atherogenesis. In vitro, a variety of enzymatic and nonenzymatic modifications of LDL can induce these reactions and thereby provide useful models for their detailed analysis. Here, we summarize current knowledge of the in vivo and in vitro modifications of LDLs leading to their aggregation, fusion, and lipid droplet formation; outline the techniques used to study these reactions; and propose a molecular mechanism that underlies these pro-atherogenic processes. Such knowledge is essential in identifying endogenous and exogenous factors that can promote or prevent LDL aggregation and fusion in vivo and to help establish new potential therapeutic targets to decelerate or even block these pathogenic reactions.https://doi.org/10.1515/bmc-2013-0016early events in atherosclerosishydrophobic interactionslipoprotein hydrolysislow-density lipoprotein (ldl) fusion kineticsthermal, chemical, and mechanical denaturation |
| spellingShingle | Lu Mengxiao Gursky Olga Aggregation and fusion of low-density lipoproteins in vivo and in vitro Biomolecular Concepts early events in atherosclerosis hydrophobic interactions lipoprotein hydrolysis low-density lipoprotein (ldl) fusion kinetics thermal, chemical, and mechanical denaturation |
| title | Aggregation and fusion of low-density lipoproteins in vivo and in vitro |
| title_full | Aggregation and fusion of low-density lipoproteins in vivo and in vitro |
| title_fullStr | Aggregation and fusion of low-density lipoproteins in vivo and in vitro |
| title_full_unstemmed | Aggregation and fusion of low-density lipoproteins in vivo and in vitro |
| title_short | Aggregation and fusion of low-density lipoproteins in vivo and in vitro |
| title_sort | aggregation and fusion of low density lipoproteins in vivo and in vitro |
| topic | early events in atherosclerosis hydrophobic interactions lipoprotein hydrolysis low-density lipoprotein (ldl) fusion kinetics thermal, chemical, and mechanical denaturation |
| url | https://doi.org/10.1515/bmc-2013-0016 |
| work_keys_str_mv | AT lumengxiao aggregationandfusionoflowdensitylipoproteinsinvivoandinvitro AT gurskyolga aggregationandfusionoflowdensitylipoproteinsinvivoandinvitro |