HDL-associated proteins affecting CVD and systemic inflammation

Area of Science:

• Cardiovascular Science
• Immunology
• Metabolic Research

Background:

• Elevated high-density lipoprotein cholesterol (HDL-C) is not a reliable indicator of protection against cardiovascular disease (CVD) and inflammation.
• Understanding HDL's functional capacity requires examining its associated proteins.

Purpose of the Study:

• To review recent advances in understanding how HDL function is modulated by associated proteins.
• To demonstrate that protein-associated HDL function is a more appropriate measure of HDL's protective capacity against CVD and inflammation.

Main Methods:

• Review of recent publications and mechanistic studies.
• Analysis of the roles of apolipoprotein M (ApoM), apolipoprotein A-I (ApoA-I), serum amyloid albumin (SAA), and scavenger receptor class B type 1 (SR-B1).
• Investigation of HDL's interaction with low-density lipoprotein (LDL), endotoxins, and inflammatory pathways.

Main Results:

• An inverse relationship exists between ApoM and clinical outcomes in chronic kidney disease and associated cardiovascular conditions.
• ApoM regulates mitochondrial function and autophagy, contributing to its protective effects.
• ApoA-I, SAA, and SR-B1 are key regulators of atherogenesis, preventing LDL deposition in arteries.
• HDL-mediated degradation of endotoxins via the endosome-lysosome pathway attenuates IL-1β activation.
• Cholesterol ester transfer protein (CETP) inhibition improved mortality in a mouse model of sepsis, indicating therapeutic potential.

Conclusions:

• HDL's regulation of inflammation and CVD involves mechanisms beyond reverse cholesterol transport.
• Key mechanisms include modulation of autophagy, prevention of LDL deposition, and endotoxin clearance.
• Associated proteins are critical determinants of HDL's cardioprotective and anti-inflammatory functions.