Apolipoprotein A-IMilano. Correlation between high density lipoprotein subclass distribution and triglyceridemia

Area of Science:

• Lipid Metabolism
• Cardiovascular Genetics
• Biochemistry

Background:

• Apolipoprotein A-IMilano (apo A-IM) variant carriers exhibit unique lipid profiles, including low HDL and variable hypertriglyceridemia.
• These carriers show a reduced prevalence of atherosclerotic vascular disease, suggesting a protective mechanism.

Purpose of the Study:

• To investigate the distribution of high-density lipoprotein (HDL) subfractions in apo A-IM carriers.
• To determine the correlation between HDL subclass abnormalities and alterations in triglyceride transport.

Main Methods:

• Sera from 24 apo A-IM carriers (A-IM+) and matched controls (A-IM-) were analyzed using rate zonal ultracentrifugation.
• HDL subclasses in 10 A-IM+ subjects were further resolved by particle size using gradient gel electrophoresis (GGE).

Main Results:

• A-IM+ subjects displayed significantly reduced HDL3 mass, altered composition, and near absence of HDL2.
• GGE revealed a unique HDL pattern in carriers with a distinct peak in the (HDL3b)gge interval, not observed in controls.
• Three distinct HDL subclass patterns were identified in carriers, correlating with plasma triglyceride and HDL cholesterol levels.

Conclusions:

• The study confirms a relationship between triglyceride transport abnormalities and altered HDL subclass distribution in apo A-IM carriers.
• These findings offer insights into the variable atherosclerotic risk observed in hypertriglyceridemic individuals.