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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:7.)
© 2006 American Heart Association, Inc.

Editorials

HIV Protease Inhibitors and Hyperlipidemia

A Fatty Acid Connection

Arthur A. Spector

From the Departments of Biochemistry and Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City.

Correspondence to Arthur A. Spector, Department of Biochemistry 4-403 BSB, University of Iowa, Iowa City, IA 52242. E-mail arthur-spector@uiowa.edu

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

Treatment with a combination of highly active antiretroviral agents considerably reduces the morbidity and mortality of human immunodeficiency virus (HIV) infection.¹ Although the clinical benefits are considerable, the protease inhibitors contained in these antiretroviral regimens produce a lipodystrophy syndrome characterized by changes in body fat distribution, hyperlipidemia, and insulin resistance.² The hyperlipidemia is attributable to increases in very low density lipoproteins (VLDL) and intermediate density lipoproteins (IDL), and it can produce serious cardiovascular complications including endothelial dysfunction and atherosclerosis.^3,4

See page 124

A number of studies indicate that the hyperlipidemia produced by HIV protease inhibitors is attributable to an increase in VLDL production. Data from HIV positive patients indicate that excessive free fatty acid (FFA) mobilization occurs because of insulin resistance in the adipose tissue,⁵ resulting in increased VLDL–triglyceride production and apoB synthesis. Likewise, studies in C57BL/6 mice treated with HIV protease inhibitors demonstrate increased VLDL-triglyceride production and apoB synthesis,⁶ and increased triglyceride synthesis also was observed in HepG₂ cells and AKR/J mice incubated with protease inhibitors.⁷ The hyperlipidemia in the mice was attributed to elevated fatty acid and cholesterol synthesis in the liver and adipose tissue caused by activation of sterol regulatory element binding protein (SREBP) 1 and 2,⁸ whereas studies in cultured liver cells suggest that the mechanism involves decreased degradation of nascent apoB attributable to inhibition of the 20S proteasome.⁹

There is also evidence that HIV protease inhibitors do not reduce the clearance of either VLDL or triglyceride-rich lipoprotein remnants,^5,6,10 providing additional support for a mechanism based . . . [Full Text of this Article]

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