Thermal behavior of human plasma high density lipoprotein

Area of Science:

• Lipid biochemistry
• Structural biology
• Biophysics

Background:

• Low-density lipoprotein (LDL) exhibits a reversible thermal transition due to cholesterol ester phase changes.
• Understanding high-density lipoprotein (HDL) thermal behavior is crucial for comprehending its structural integrity and lipid transport functions.

Purpose of the Study:

• To investigate whether HDL cholesterol esters display similar thermal transitions as observed in LDL.
• To elucidate the thermal stability and disruption mechanisms of HDL structure.

Main Methods:

• Differential scanning calorimetry (DSC) to detect thermal transitions.
• Low-angle X-ray scattering to analyze lipid phase organization.
• Polarizing microscopy to visualize liquid crystalline phases.

Main Results:

• Neither HDL2 nor HDL3 showed thermal transitions between 0–60°C, unlike LDL.
• Isolated HDL cholesterol esters and mixtures exhibited liquid crystalline transitions at 20–40°C.
• HDL disruption above 60°C involved selective apolipoprotein A-1 release, followed by generalized disruption with cholesterol ester and apolipoprotein A-2 release.
• Post-disruption, HDL cholesterol esters showed liquid crystalline transitions, indicating the formation of large domains.

Conclusions:

• The absence of cholesterol ester transitions in intact HDL suggests interactions with the protein-phospholipid surface inhibit lipid phase organization.
• Apolipoprotein A-1 plays a lesser role than apolipoprotein A-2 in maintaining the stability of HDL's apolar lipid core.
• HDL's thermal behavior reveals distinct structural stability mechanisms compared to LDL.