For decades high-density lipoproteins (HDL) and HDL-cholesterol (HDL-C) levels were viewed as synonymous and modulation of HDL-C levels by drug therapy held great promise for the prevention and treatment of cardiovascular disease. Nevertheless, recent failures of drugs that raise HDL-C to reduce cardiovascular risk and the now greater understanding of the complexity of HDL composition and biology have prompted researchers in the field to redefine HDL. As such, the focus of HDL has now started to shift away from a cholesterol centric view towards HDL particle number, subclasses, and other alternative metrics of HDL. Many of the recently discovered functions of HDL are, in fact, not strictly conferred by its ability to promote cholesterol flux, but by the other molecules it transports, including a diverse set of proteins, small RNAs, hormones, carotenoids, vitamins, and bioactive lipids. Based on the ability of HDL to interact with almost all cells and transport and deliver fat-soluble cargo, HDL has the remarkable capacity to affect a wide-variety of endocrine-like systems. Here in this review, we characterize the unique cargo on HDL and address the functional relevance and consequences of HDL transport and delivery of non-cholesterol molecules to recipient cells and tissues.
This article first Published on March 19, 2013, doi: 10.1194/jlr.R035964 The Journal of Lipid Research, jlr.R035964.
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