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Updated: Jul 7, 2026
05:48
Rapid Generation of Amyloid from Native Proteins In vitro
Published on: December 5, 2013
Low density lipoprotein misfolding and amyloidogenesis
Tiziana Parasassi1, Marco De Spirito, Giampiero Mei
1Istituto di Neurobiologia e Medicina Molecolare, CNR, Via del Fosso del Cavaliere 100, 00133 Rome, Italy. t.parasassi@inmm.cnr.it
Summary
Electronegative LDL (LDL[-]) apoprotein misfolding initiates LDL aggregation, mimicking protein amyloidogenesis. This process forms globules similar to early atherogenesis droplets, suggesting a novel mechanism in artery wall injury.
Area of Science:
- Biochemistry
- Molecular Biology
- Cardiovascular Research
Background:
- Early atherogenesis involves subendothelial lipid droplet accumulation and inflammation, leading to foam cell and plaque formation.
- Low-density lipoprotein (LDL) is the primary component of these lipid droplets, with modification preceding their retention.
- Electronegative LDL (LDL[-]) is a modified LDL form found in plasma, associated with cardiovascular risk biomarkers.
Purpose of the Study:
- To investigate the modification of LDL apoprotein in LDL(-) and its role in LDL aggregation.
- To characterize the structural changes and aggregation process of LDL.
- To determine if LDL modification can trigger an inflammatory response in the artery wall.
Main Methods:
- Identification and characterization of electronegative LDL (LDL[-]).
- Light scattering and atomic force microscopy to observe LDL aggregation.
- Ellipticity and tryptophan fluorescence measurements to monitor protein misfolding.
- Computational analysis of apoprotein primary sequence.
Main Results:
- LDL(-) apoprotein misfolding primes native LDL for aggregation, resembling protein amyloidogenesis.
- LDL aggregation proceeds via intermediate globules, similar to those found in atheromatous lesions.
- Misfolding spreads domino-style from LDL(-) to all LDL particles during aggregation.
- Computational analysis identified an aggregation-prone domain in the apoprotein's alpha2 region.
Conclusions:
- Apoprotein misfolding in LDL(-) is a critical LDL modification that triggers LDL aggregation.
- This aggregation process generates structures similar to early atherogenesis lipid droplets.
- Modified LDL, through apoprotein misfolding and aggregation, acts as a trigger for the artery wall's response-to-injury.
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