The double jeopardy of HDL

Area of Science:

• Cardiovascular Science
• Immunology
• Lipid Metabolism

Background:

• High-density lipoprotein (HDL) is crucial for cholesterol efflux, a key factor in cardiovascular disease protection.
• Emerging evidence highlights HDL's anti-inflammatory properties, suggesting a dual role in cardiovascular health.
• HDL's immune function varies, inhibiting inflammation during normal conditions but promoting it during an acute phase response (APR).

Purpose of the Study:

• To investigate the relationship between HDL's inflammatory properties and its cholesterol efflux capacity.
• To explore the role of HDL structure and function in predicting cardiovascular disease risk.
• To examine HDL's inflammatory status in humans with coronary heart disease (CHD) before and after statin therapy.

Main Methods:

• Comparison of HDL inflammatory profiles in atherosclerosis-susceptible versus resistant mouse strains.
• Analysis of HDL inflammatory status and cholesterol efflux in human subjects with CHD.
• Investigation of the impact of oxidative alterations on apolipoprotein A-I (apoA-I) function.

Main Results:

• Atherosclerosis-resistant mice possess anti-inflammatory HDL, while susceptible strains have pro-inflammatory HDL.
• Humans with CHD exhibited pro-inflammatory HDL, which persisted in some after statin therapy.
• Pro-inflammatory HDL demonstrated weaker cholesterol efflux capacity compared to anti-inflammatory HDL.
• Oxidative damage to apoA-I impaired HDL's cholesterol efflux function.

Conclusions:

• HDL's inflammatory properties and cholesterol efflux capacity are closely linked.
• HDL structure and function, rather than just HDL-cholesterol levels, are critical determinants of cardiovascular disease risk.
• Targeting HDL's functional and structural integrity may offer novel therapeutic strategies for cardiovascular disease.