New targets of high-density lipoprotein therapy.
OBJECTIVE
Increasing attention has focused on the development of therapeutic strategies to promote the biologic activity of HDL particles, which possess a number of functional properties that contribute to their role in cardioprotection. Currently available therapies raise levels of HDL-cholesterol by relatively modest amounts. This review describes experimental strategies that promote HDL activity.


RESULTS
The functional quality of HDL may be more important than the absolute level of HDL-cholesterol found in the systemic circulation. This is supported by the observation that small rises in HDL-cholesterol with current therapies is associated with clinical benefit. This has major implications for the development of new therapies. A number of therapeutic strategies have been developed that promote reverse cholesterol transport, inhibit inflammatory events in the vessel wall, and modify remodeling of HDL particles within the systemic circulation.


CONCLUSIONS
A number of emerging therapies appear to promote the biologic activity of HDL. These agents can be administered as acute infusions in the setting of acute ischemic syndromes or as oral therapy for chronic prevention of cardiovascular disease.
Nicholls
Stephen J
SJ
Department of Cardiovascular Medicine, Center for Cardiovascular Diagnostics and Prevention, Cleveland Clinic, Cleveland, Ohio 44195, USA. nichols1@ccf.org
Nissen
Steven E
SE
D000284:Administration, Oral; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D050197:Atherosclerosis / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000517:prevention & control*; D002784:Cholesterol / Q000378:metabolism; D053480:Cholesterol Ester Transfer Proteins / Q000378:metabolism; D008076:Cholesterol, HDL / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000819:agonists; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism*; D000071518:Liver X Receptors; D008954:Models, Biological; D057093:Orphan Nuclear Receptors; D010455:Peptides / Q000737:chemistry; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists; D012307:Risk Factors
D000924:Anticholesteremic Agents; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D004268:DNA-Binding Proteins; D008075:Lipoproteins, HDL; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D010455:Peptides; D018160:Receptors, Cytoplasmic and Nuclear; D002784:Cholesterol