Epidemiological studies during the last five years suggest that a relation between high density lipoprotein cholesterol (HDL-C) levels and the risk for cardiovascular disease (CVD) does exist but follows rather a "U-shaped" curve with an optimal range of HDL-C concentration between 40 and 70 mg/dl for men and 50-70 mg/dl for women. Moreover, as research in the field of lipoproteins progresses it becomes increasingly apparent that HDL particles possess different attributes and depending on their structural and functional characteristics, they may be "antiatherogenic" or "proatherogenic". In light of this information, it is highly doubtful that the choice of experimental drugs and the design of respective clinical trials that put the HDL-C raising hypothesis at test, were the most suitable. Here, we compile the existing literature on HDL, providing a critical up-to-date view that focuses on key data from the biochemistry, epidemiology and pharmacology of HDL, including data from clinical trials. We also discuss the most up-to-date information on the contribution of HDL structure and function to the prevention of atherosclerosis. We conclude by summarizing important differences between mouse models and humans, that may explain why pharmacological successes in mice turn out to be failures in humans.
Keywords: Atherosclerosis; Coronary heart disease; Function; High density lipoprotein; Structure.
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