Thursday

HDL functionality in reverse cholesterol transport--Challenges in translating data emerging from mouse models to human disease

Abstract

Whereas LDL-derived cholesterol accumulates in atherosclerotic lesions, HDL particles are thought to facilitate removal of cholesterol from the lesions back to the liver thereby promoting its fecal excretion from the body. Because generation of cholesterol-loaded macrophages is inherent to atherogenesis, studies on the mechanisms stimulating the release of cholesterol from these cells and its ultimate excretion into feces are crucial to learn how to prevent lesion development or even induce lesion regression.

Modulation of this key anti-atherogenic pathway, known as the macrophage-specific reverse cholesterol transport, has been extensively studied in several mouse models with the ultimate aim of applying the emerging knowledge to humans.

The present review provides a detailed comparison and critical analysis of the various steps of reverse cholesterol transport in mouse and man. We attempt to translate this in vivo complex scenario into practical concepts, which could serve as valuable tools when developing novel HDL-targeted therapies.

2016 Jul;1861(7):566-83. doi: 10.1016/j.bbalip.2016.03.004. Epub 2016 Mar 9.

Monday

Review: The Changing Face of HDL and the Best Way to Measure It.

Abstract

BACKGROUND:

HDL cholesterol (HDL-C) is a commonly used lipid biomarker for assessing cardiovascular health. While a central focus has been placed on the role of HDL in the reverse cholesterol transport (RCT) process, our appreciation for the other cardioprotective properties of HDL continues to expand with further investigation into the structure and function of HDL and its specific subfractions. The development of novel assays is empowering the research community to assess different aspects of HDL function, which at some point may evolve into new diagnostic tests.

CONTENT:

This review discusses our current understanding of the formation and maturation of HDL particles via RCT, as well as the newly recognized roles of HDL outside RCT. The antioxidative, antiinflammatory, antiapoptotic, antithrombotic, antiinfective, and vasoprotective effects of HDL are all discussed, as are the related methodologies for assessing these different aspects of HDL function. We elaborate on the importance of protein and lipid composition of HDL in health and disease and highlight potential new diagnostic assays based on these parameters.

SUMMARY:

Although multiple epidemiologic studies have confirmed that HDL-C is a strong negative risk marker for cardiovascular disease, several clinical and experimental studies have yielded inconsistent results on the direct role of HDL-C as an antiatherogenic factor. As of yet, our increased understanding of HDL biology has not been translated into successful new therapies, but will undoubtedly depend on the development of alternative ways for measuring HDL besides its cholesterol content.
PMID:
27879324
DOI:
10.1373/clinchem.2016.257725