Current concept of reverse cholesterol transport and novel strategy for atheroprotection

Area of Science:

• Cardiovascular Medicine
• Biochemistry
• Pharmacology

Background:

• Elevated low-density lipoprotein cholesterol (LDL-C) is a major risk factor for coronary heart disease (CHD).
• Statin therapy effectively reduces cardiovascular events but leaves significant residual risk.
• Low high-density lipoprotein cholesterol (HDL-C) is independently associated with increased CHD risk, even during statin treatment.

Purpose of the Study:

• To review the role of HDL-C in reverse cholesterol transport.
• To discuss novel HDL-targeting therapeutic strategies for residual cardiovascular risk.
• To explore the potential of microRNA manipulation in HDL-based therapies.

Main Methods:

• Literature review of studies on HDL-C function and therapeutic targets.
• Analysis of recent clinical trial outcomes for HDL-raising therapies.
• Summary of emerging strategies for modulating HDL functionality.

Main Results:

• While lowering LDL-C reduces cardiovascular events, residual risk persists.
• Simply increasing HDL-C levels has not yielded satisfactory clinical benefits.
• HDL-C functionality, particularly its role in reverse cholesterol transfer, is crucial.

Conclusions:

• Functional HDL-C, rather than just elevated levels, is a more promising therapeutic target.
• Novel strategies targeting HDL functionality are needed to address residual cardiovascular risk.
• MicroRNA-based approaches represent a potential avenue for HDL-targeting therapies.