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High density lipoproteins and extracellular vesicles-distinct but overlapping circulating particles and their role in
Linas Černiauskas1,2, Goda Aleknavičiūtė1,2, Skaistė Arbačiauskaitė3,4
1Department of Physiology, Biochemistry, Microbiology and Laboratory Medicine, Institute of Biomedical Sciences, Vilnius University, Vilnius, Lithuania.
Insights
High-density lipoproteins (HDL) and extracellular vesicles (EVs) share overlapping features, complicating their isolation and study in atherosclerosis. This review compares their roles in cardiovascular disease, exploring methodological challenges and potential biological interactions.
Area of Science:
- Cardiovascular Biology
- Nanomedicine
- Biochemistry
Background:
- Cardiovascular disease (CVD) is a major global health issue, with atherosclerosis as its primary cause.
- High-density lipoproteins (HDL) and extracellular vesicles (EVs) are key circulating particles involved in lipid metabolism, inflammation, and thrombosis relevant to atherosclerosis.
- HDLs and EVs exhibit overlapping physicochemical properties, making their separation difficult and potentially confounding research findings.
Purpose of the Study:
- To compare the structural, biophysical, and functional characteristics of HDLs and EVs in the context of atherosclerosis.
- To review the biogenesis pathways and molecular cargo of HDLs and EVs.
- To discuss the implications of HDL-EV overlap for research and potential biological interactions.
Main Methods:
- Literature review and comparative analysis of existing studies on HDLs and EVs.
- Examination of structural and biophysical properties, including size, density, and molecular composition.
- Evaluation of functional roles in endothelial activation, inflammation, lipid handling, and thrombosis.
Main Results:
- HDLs and EVs share overlapping density and size ranges, posing technical challenges for isolation.
- Both particle types contribute to key processes in atherosclerosis, including inflammation and cholesterol transport.
- Distinct biological roles and origins exist despite shared features, necessitating careful interpretation of co-isolated fractions.
Conclusions:
- The overlap between HDLs and EVs presents methodological hurdles in atherosclerosis research.
- Understanding the distinct and potentially interactive roles of HDLs and EVs is crucial for advancing CVD therapies.
- Further investigation is needed to determine if HDL-EV overlap reflects co-isolation or biologically relevant interactions in circulating nanoparticle networks.
Abstract:
Cardiovascular disease remains the leading cause of morbidity and mortality worldwide, with atherosclerosis representing its principal pathological basis. High-density lipoproteins (HDL) and extracellular vesicles (EVs) are abundant circulating particles implicated in lipid metabolism, vascular inflammation, intercellular communication, and thrombotic processes relevant to atherosclerosis. Although HDLs and EVs differ in origin, structure, biogenesis, and canonical function, they share overlapping physicochemical and molecular features. Their density ranges substantially overlap, and small EV populations may approach the upper size range of HDL particles, making their separation from plasma technically challenging. As a result, common isolation workflows may generate HDL-enriched or EV-enriched fractions rather than fully particle-specific preparations, complicating the interpretation of proteomic, lipidomic, nucleic acid, and functional studies. This review compares the structural and biophysical characteristics, biogenesis pathways, molecular cargo, and atherosclerosis-related functions of HDLs and EVs. We highlight how both particle classes contribute to endothelial activation, inflammation, cholesterol handling, foam cell formation, plaque progression, and thrombosis, while also emphasizing their distinct biological roles. Finally, we discuss whether HDL-EV overlap should be interpreted solely as methodological co-isolation or may also reflect biologically relevant interactions within circulating nanoparticle networks in atherosclerosis.
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