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Updated: May 1, 2026

Isolation and Analysis of Plasma Lipoproteins by Ultracentrifugation
Published on: January 28, 2021
Subfractions and subpopulations of HDL: an update
1Biomedical Department of Internal Medicine and Medical Specialties (DiBiMIS), University of Palermo, Via del Vespro, 141, 90127, Palermo, Italy. manfredi.rizzo@unipa.it.
Insights
High-density lipoproteins (HDL) exhibit diverse functions beyond cholesterol transport. Understanding HDL subclasses and their functionality is key for predicting and potentially reducing cardiovascular risk.
Area of Science:
- Cardiovascular Science
- Lipid Metabolism
- Biochemistry
Background:
- High-density lipoproteins (HDL) are recognized for their atheroprotective role, primarily through reverse cholesterol transport (RCT).
- HDLs possess diverse biological activities including antioxidant, anti-inflammatory, cytoprotective, vasodilatory, antithrombotic, and anti-infectious properties.
- Significant structural, metabolic, and biological heterogeneity exists among HDL particles, leading to various subclasses.
Purpose of the Study:
- To review recent findings on the atheroprotective and functional characteristics of different HDL subfractions.
- To provide an overview of methods used for separating HDL subfractions.
- To discuss the potential of HDL subclasses as biomarkers and therapeutic targets for cardiovascular risk.
Main Methods:
- Literature review of studies investigating HDL subclasses and their functions.
- Analysis of evidence regarding HDL modification and its impact on atherogenicity.
- Overview of current techniques for HDL subfraction separation.
Main Results:
- Different HDL subfractions and separation techniques yield varying associations with atheroprotection and cardiovascular risk.
- HDL particle modification, particularly in proteins and lipids, can impair protective functions and induce proatherogenic properties, especially in inflammatory states.
- HDL functionality appears to be a more promising therapeutic target than HDL cholesterol quantity, though optimal subfractions remain debated.
Conclusions:
- HDL subclasses are emerging as important biomarkers for predicting and reducing cardiovascular risk.
- Further research is needed to establish a 'gold standard' separation method and identify reliable HDL subfractions for risk assessment and therapeutic targeting.
- Focusing on HDL functionality and specific subfractions may lead to more effective cardiovascular therapies.
Abstract:
High-density lipoproteins (HDL) are classified as atheroprotective because they are involved in transport of cholesterol to the liver, known as "reverse cholesterol transport (RCT)" exerting antioxidant and anti-inflammatory activities. There is also evidence for cytoprotective, vasodilatory, antithrombotic, and anti-infectious activities for these lipoproteins. HDLs are known by structural, metabolic and biologic heterogeneity. Thus, different methods are able to distinguish several subclasses of HDL. Different separation techniques appear to support different HDL fractions as being atheroprotective or related with lower cardiovascular (CV) risk. However, HDL particles are not always protective. Modification of constituents of HDL particles (primarily in proteins and lipids) can lead to the decrease in their activity and induce proatherogenic properties, especially when isolated from patients with augmented systemic inflammation. According to available studies, it seems that HDL functionality may be a better therapeutic target than HDL cholesterol quantity; however, it is still disputable which subfractions are most beneficial. There is mounting evidence supporting HDL subclasses as an important biomarker to predict and/or reduce CV risk. In this review we discuss recent notices on atheroprotective and functional characteristic of different HDL subfractions. Also, we provide a brief overview of the different methods used by clinicians and researchers to separate HDL subfractions. Ongoing and future investigations will yield important new information if any given separation method might represent a 'gold standard', and which subfractions are reliable markers of CV risk and/or potential targets of novel, more focused, and effective therapies.
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