Insights to HDL dysfunctionality: hypothesis of exhausted HDL.

Area of Science:

• Cardiovascular Science
• Lipoprotein Metabolism
• Atherosclerosis Research

Background:

• High-density lipoprotein (HDL) traditionally viewed as protective against cardiovascular disease.
• Emerging evidence shows HDL can become dysfunctional (dys-HDL), contributing to cardiovascular disease and diabetes.
• Dysfunctional HDL paradoxically promotes atherosclerosis, a key factor in cardiovascular mortality.

Purpose of the Study:

• To clarify the broad concept of dysfunctional HDL (dys-HDL).
• To distinguish between HDL with diminished protective function and actively proatherogenic HDL.
• To introduce the concept of 'exhausted' HDL (ex-HDL) as an intermediate state.

Main Methods:

• Literature review on HDL functionality and dysfunction.
• Conceptual analysis of HDL's transition from protective to proatherogenic states.
• Hypothetical classification of dys-HDL into ex-HDL and proatherogenic HDL.

Main Results:

• HDL can transition from a protective role to a proatherogenic one.
• A spectrum of HDL dysfunction exists, from partially impaired to actively harmful.
• Proposed classification distinguishes 'exhausted' HDL (ex-HDL) from fully proatherogenic HDL.

Conclusions:

• Understanding HDL dysfunction is crucial for cardiovascular risk management.
• The proposed classification of dys-HDL (ex-HDL and proatherogenic HDL) may enable targeted therapies.
• Further research into ex-HDL could elucidate mechanisms of cardiovascular disease progression.