Beyond the genetics of HDL: why is HDL cholesterol inversely related to cardiovascular disease?

Area of Science:

• Cardiovascular Science
• Metabolic Research
• Molecular Biology

Background:

• Plasma high-density lipoprotein (HDL) cholesterol levels show an inverse association with cardiovascular disease (CVD) risk.
• Numerous factors influencing HDL cholesterol have been identified through family and genetic studies, yet the underlying reasons for the inverse relationship remain unclear.
• Evidence suggests HDL loses its protective function in patients at high CVD risk, and simply increasing HDL cholesterol content may not be effective.

Purpose of the Study:

• To review recent molecular studies on HDL metabolism.
• To explore the intricate relationships between HDL, triglyceride, and glucose metabolism.
• To identify potential therapeutic targets for conditions like type 2 diabetes and metabolic syndrome.

Main Methods:

• Review of molecular studies and genome-wide association studies (GWAS) from recent years.
• Analysis of factors controlling HDL cholesterol levels.
• Examination of the functional properties of HDL in different patient populations.

Main Results:

• While many factors affecting HDL cholesterol are known, the precise mechanisms linking HDL to CVD risk are not fully resolved.
• HDL in patients at increased CVD risk often exhibits diminished protective properties.
• Recent findings highlight complex interdependencies between HDL, triglyceride, and glucose metabolism.

Conclusions:

• A reassessment of the HDL hypothesis is needed, focusing on HDL function rather than just cholesterol levels.
• Understanding the molecular regulation of HDL metabolism is key to developing new treatments for metabolic disorders.
• Simultaneous study of HDL, triglyceride, and glucose metabolism is essential.