# Thermal Remodeling of Human HDL Particles Reveals Diverse Subspecies

## TL;DR

This study reveals that human HDL particles can be divided into many distinct subspecies based on their thermal stability and structure.

## Contribution

The study identifies at least 15 new HDL subspecies through thermal remodeling and charge detection mass spectrometry.

## Key findings

- HDL subpopulations undergo structural rearrangements at distinct transition temperatures.
- At least 15 subspecies of HDL are resolved, differing in size, charge, and thermal stability.
- New structural forms within known HDL subpopulations may exist.

## Abstract

High-density
lipoproteins (HDL) are micelle-like particles
consisting
of a core of triglycerides and cholesteryl esters surrounded by a
shell of phospholipid, cholesterol, and apolipoproteins. HDL is considered
“good” cholesterol, and its concentration in plasma
is used clinically in assessing cardiovascular health. However, these
particles vary in structure, composition, and therefore function,
and thus can be resolved into subpopulations, some of which have specific
cardioprotective properties. Mass measurements of HDL by charge detection
mass spectrometry (CD-MS) previously revealed seven distinct subpopulations
which could be delineated by mass and charge [Lutomski, C. A. et al.
Anal. Chem. 2018]. Here, we investigate the thermal stabilities of
these subpopulations; upon heating, the particles within each subpopulation
undergo structural rearrangements with distinct transition temperatures.
In addition, we find evidence for many new families of structures
within each subpopulation; at least 15 subspecies of HDL are resolved.
These subspecies vary in size, charge, and thermal stability. While
this suggests that these new subspecies have unique molecular compositions,
we cannot rule out the possibility that we have found evidence for
new structural forms within the known subpopulations. The ability
to resolve new subspecies of HDL particles may be important in understanding
and delineating the role of unique particles in cardiovascular health
and disease.