HDL quality or cholesterol cargo: what really matters--spotlight on sphingosine-1-phosphate-rich HDL

Area of Science:

• Cardiovascular Research
• Biochemistry
• Atherosclerosis Research

Background:

• High-density lipoprotein cholesterol (HDL-C) levels are traditionally assessed for cardiovascular risk.
• Recent clinical trials indicate that simply increasing HDL-C levels does not improve cardiovascular outcomes.
• This suggests that HDL's functionality, beyond its cholesterol content, is critical for its atheroprotective effects.

Purpose of the Study:

• To review the evidence supporting the role of HDL-bound sphingosine-1-phosphate (S1P) in HDL's atheroprotective functions.
• To explore S1P as a potential therapeutic target for cardiovascular diseases.
• To challenge the sole reliance on absolute HDL-C levels for assessing cardiovascular risk.

Main Methods:

• Literature review of recent randomized clinical trials and emerging evidence.
• Analysis of studies investigating the functional properties of HDL.
• Focus on the association between HDL and sphingosine-1-phosphate (S1P).

Main Results:

• Large clinical trials with niacin and dalcetrapib failed to show improved cardiovascular outcomes in statin-treated patients.
• Emerging evidence implicates HDL-bound S1P in various cardioprotective functions of HDL.
• These functions include vasodilation, angiogenesis, endothelial barrier integrity, and protection against ischemia/reperfusion injury.

Conclusions:

• HDL functionality is intrinsically linked to its molecular composition.
• Sphingosine-1-phosphate (S1P) is a significant component contributing to HDL's atheroprotective properties.
• HDL-associated S1P represents a promising future therapeutic target for cardiovascular disease prevention.