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(Circulation. 2006;113:5-8.)
© 2006 American Heart Association, Inc.

Editorial

Liver X Receptor Activation and High-Density Lipoprotein Biology

A Reversal of Fortune?

Chih-Hao Lee, PhD; Jorge Plutzky, MD

From the Department of Genetics and Complex Diseases, Harvard School of Public Health (C.-H.L.); Cardiovascular Division, Brigham and Women’s Hospital (J.P.); and Donald Reynolds Center for Clinical Cardiovascular Research, Harvard Medical School (J.P.), Boston, Mass.

Correspondence to Jorge Plutzky, MD, 77 Ave Louis Pasteur, NRB 740, Boston, MA 02115. E-mail jplutzky@rics.bwh.harvard.edu

Key Words: Editorials • lipids • lipoproteins • liver X receptor • peroxisome proliferator-activated receptors

An extract of the first 250 words of the full text is provided, because this article has no abstract.

A fortunate development in medicine has been the unraveling of the relationship between LDLs and atherosclerosis, as evidenced by the dramatic impact of LDL lowering on cardiovascular events.^1,2 Risk reduction by decreasing LDL could also be considered fortuitous; average LDL levels in Western society may well be nearly double "ideal," even if "normal" or "physiological" cholesterol levels remain difficult to define. Humans typically are born with LDL levels in the 30-µg/dL range; in more agrarian societies, LDL levels average 70 to 100 mg/dL.³ Thus, the cardiovascular benefits documented over the past decade with HMG CoA reductase inhibitors (statins) have occurred through large-scale reductions of LDL by 30% to 70%.⁴ In contrast, in most cases, halving blood pressure or glucose would not be tolerated. Together, these observations support an "overflow" model in which LDL promotes atherosclerosis at levels that far outstrip any physiological role or survival advantage. Despite this, an asymptote of risk reduction may be reached once LDL levels have been lowered to currently recommended levels, leaving scientists and clinicians to look elsewhere for therapeutic opportunities to reduce the on-treatment event rate evident in statin trials, even at LDL levels well below 100 mg/dL.⁵ In this regard, HDL cholesterol (HDL) has received considerable attention given strong epidemiological data for its protective effects, encouraging clinical data with even modest HDL raising, and a rational scientific mechanism through HDL-mediated reverse cholesterol transport.⁶

Article p 90

One approach to raising HDL is to activate nuclear hormone nuclear receptors that control transcription of key . . . [Full Text of this Article]

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