The HDL hypothesis: does high-density lipoprotein protect from atherosclerosis?

Area of Science:

• Cardiovascular Science
• Lipid Metabolism
• Atherosclerosis Research

Background:

• Plasma high-density lipoprotein (HDL) cholesterol concentrations are inversely associated with cardiovascular disease (CVD) risk.
• This observation has led to the
• HDL hypothesis,
• proposing HDL's protective role against atherosclerosis.

Purpose of the Study:

• To review and critically evaluate the experimental evidence supporting the
• HDL hypothesis
• regarding HDL's atheroprotective functions.

Main Methods:

• Review of in vitro studies investigating HDL's anti-atherogenic properties.
• Analysis of animal studies and human clinical trials examining HDL's role in atherosclerosis.
• Examination of human genetic studies assessing the impact of HDL genes on cardiovascular risk.

Main Results:

• In vitro studies suggest multiple anti-atherogenic functions of HDL, but human validation is lacking.
• Animal and clinical studies provide support for HDL's atheroprotective role, often confounded by concurrent lipid alterations.
• Human genetic studies have not conclusively demonstrated that HDL genes influence cardiovascular risk.

Conclusions:

• Despite extensive research, the
• HDL hypothesis
• remains unproven.
• Further investigation is essential to definitively establish HDL's role in preventing atherosclerosis and cardiovascular disease.