High-density lipoprotein metabolism, composition, function, and deficiency.

Area of Science:

• Cardiovascular Research
• Lipid Metabolism
• Molecular Biology

Background:

• High-density lipoprotein (HDL) plays a critical role in reverse cholesterol transport and cardiovascular health.
• Understanding HDL composition and function is essential for developing effective strategies against coronary heart disease (CHD).
• Genetic mutations affecting key HDL-related proteins can lead to severe metabolic disorders and premature CHD.

Purpose of the Study:

• To review recent advancements in HDL metabolism, composition, and function.
• To explore the impact of HDL deficiency states caused by genetic mutations.
• To examine the relationship between HDL and coronary heart disease (CHD).

Main Methods:

• Review of current scientific literature on HDL metabolism and function.
• Analysis of genetic studies investigating mutations in apolipoprotein (apo) A-I, ATP-binding cassette transfer protein A1, and lecithin cholesterol acyltransferase (LCAT) genes.
• Examination of the protein complex within HDL, including apoA-I, myeloperoxidase (MPO), and paraoxonase 1 (PON1).

Main Results:

• The HDL complex includes apoA-I, MPO, and PON1, which are critical for HDL binding and function.
• MPO negatively impacts HDL function, while PON1 has a beneficial effect.
• Deficiencies in apoA-I, ATP-binding cassette transfer protein A1, or LCAT lead to premature CHD, hepatosplenomegaly, neuropathy, or kidney failure, with reported heterogeneity.

Conclusions:

• Proteins beyond apoA-I and apoA-II, such as MPO and PON1, significantly influence HDL function.
• Substantial progress has been made in understanding HDL protein content and its functional implications.
• Further research into HDL composition and function may reveal new therapeutic targets for cardiovascular diseases.