High-density lipoproteins from human alcoholics exhibit impaired reverse cholesterol transport function

Area of Science:

• Biochemistry
• Cardiovascular Science
• Metabolic Disorders

Background:

• Chronic alcohol consumption is known to affect lipid metabolism.
• Apolipoprotein E (apo E) is crucial for reverse cholesterol transport (RCT) and high-density lipoprotein (HDL) function.
• Previous research indicated alcohol inhibits apo E sialylation, impairing its binding to HDL.

Purpose of the Study:

• To investigate the impact of chronic alcohol consumption on the RCT function of HDL.
• To compare HDL function in non-drinkers, chronic alcoholics (ALC), and chronic alcoholics with liver disease (ALD).
• To determine if alcohol itself or liver disease exacerbates the impairment of HDL's RCT function.

Main Methods:

• Isolated HDL from plasma of non-drinkers (n=9), ALC (n=8), and ALD (n=6).
• Assessed HDL cholesterol efflux capacity using [3H]cholesterol oleate-preloaded mouse macrophages.
• Evaluated HDL's ability to deliver cholesterol to HepG2 cells in culture.

Main Results:

• HDL cholesterol efflux capacity was significantly reduced (83-84%) in both ALC and ALD groups compared to non-drinkers.
• HDL's capacity to deliver cholesterol to the liver decreased by 54% in ALC and 64% in ALD.
• Plasma apo E/apo A1 ratio decreased by 31-32% in both ALC and ALD groups.

Conclusions:

• Chronic alcohol consumption significantly impairs the reverse cholesterol transport function of HDL.
• Alcohol per se, not necessarily liver disease, is responsible for the detrimental effects on HDL's RCT function.
• Ethanol-induced desialylation of apo E adversely affects HDL's association with apo E, compromising RCT.