Electronegative Low-Density Lipoprotein Dynamics in Cardiovascular Disease
Summary
Low-density lipoprotein (LDL) is a central mediator of atherosclerotic cardiovascular disease. Among its heterogeneous subfractions, electronegative LDL—characterised by an increased negative surface charge arising from oxidative and other chemical modifications—exhibits distinct pro-atherogenic properties. These modified particles interact preferentially with scavenger receptors such as LOX-1 on endothelial cells and macrophages, triggering inflammatory signalling, oxidative stress and endothelial dysfunction. Electronegative LDL promotes DNA damage responses in the vascular wall, induces senescence of endothelial progenitor cells, and fosters foam cell formation via enhanced lipid uptake and intracellular triglyceride accumulation. Clinically, elevated proportions of electronegative LDL are associated with plaque vulnerability, stenotic lesions and adverse outcomes in acute coronary syndromes. Emerging lipidomic analyses reveal that shifts in lipid composition within electronegative subfractions further amplify their pathogenic potential. Together, mechanistic and translational studies underscore electronegative LDL as both a mediator and a biomarker of disease activity, with global implications for risk stratification and tailored therapeutic interventions targeting modified lipoproteins.
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Electronegative Low-Density Lipoprotein Dynamics in Cardiovascular Disease publication trend
The graph below shows the total number of articles in electronegative low-density lipoprotein dynamics in cardiovascular disease across all publications each year (not limited to Nature Index journals).
Technical terms
Electronegative LDL: A subfraction of low-density lipoprotein particles with increased negative surface charge due to oxidative or other chemical modifications, associated with enhanced atherogenicity.
LOX-1: Lectin-like oxidised LDL receptor-1, a scavenger receptor on endothelial and immune cells that mediates uptake of oxidised and electronegative LDL and activates pro-inflammatory pathways.
Plaque vulnerability: The propensity of an atherosclerotic plaque to rupture, characterised by a large lipid core, thin fibrous cap and intraplaque neovascularisation, leading to thrombosis.
Lipidomics: Comprehensive profiling of lipid species within a biological sample, used to elucidate changes in lipid composition of lipoprotein subfractions under pathological conditions.
References
- Electronegative LDL Is Associated with Plaque Vulnerability in Patients with Ischemic Stroke and Carotid Atherosclerosis. Antioxidants (2023).
- Low-density lipoprotein electronegativity and risk of death after acute coronary syndromes: A case-cohort analysis. Atherosclerosis (2023).
- Electronegative LDL: A Circulating Modified LDL with a Role in Inflammation. Mediators of Inflammation (2013).
- Electronegative LDL Promotes Inflammation and Triglyceride Accumulation in Macrophages. Cells (2020).
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