High-density lipoproteins: multifunctional vanguards of the cardiovascular system

Area of Science:

• Cardiovascular Science
• Lipid Metabolism
• Molecular Biology

Background:

• Plasma high-density lipoprotein (HDL)-cholesterol levels show an inverse correlation with coronary artery disease (CAD), a leading global cause of mortality.
• HDL particles facilitate reverse cholesterol transport from peripheral tissues to the liver and influence various vascular processes, including vasomotor function and endothelial cell behavior.
• Genetic disorders affecting HDL have provided crucial insights into the role of HDL particles, with some mutations linked to premature CAD and others to longevity.

Purpose of the Study:

• To explore the multifaceted roles of high-density lipoprotein (HDL) particles in cardiovascular health and disease.
• To review the impact of genetic variations on HDL function and its association with coronary artery disease.
• To discuss current and potential therapeutic strategies targeting HDL metabolism for cardiovascular disease management.

Main Methods:

• Review of existing literature on HDL cholesterol, its inverse correlation with coronary artery disease, and its vascular effects.
• Analysis of molecular mechanisms underlying HDL particle function, including lipid exchange and signaling pathways.
• Examination of genetic disorders of HDL and their clinical implications.
• Evaluation of current and emerging therapeutic interventions aimed at modulating HDL metabolism.

Main Results:

• HDL particles play a critical role in reverse cholesterol transport and possess atheroprotective properties by modulating vascular functions.
• Genetic mutations affecting HDL can lead to HDL deficiency and premature coronary artery disease, or paradoxically, may be associated with increased longevity.
• Current therapies like fibrates, statins, and niacin impact HDL metabolism, while novel strategies target specific pathways and molecules.

Conclusions:

• Therapeutic modulation of HDL metabolism requires consideration of particle composition, size, and charge, not just cholesterol content.
• Targeting pathways such as cholesteryl ester transfer protein (CETP) inhibition, ATP-binding cassette A1 (ABCA1) transporter modulation, and scavenger receptor-B1 (SR-B1) offers promising avenues for cardiovascular disease treatment.
• Emerging therapies, including apolipoprotein AI (ApoA-I) injection and oral peptides, aim to mimic HDL's beneficial biological effects.