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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:1758.)
© 2002 American Heart Association, Inc.

Editorials

HIV Therapies and Atherosclerosis

Answers or Questions?

Nageswara R. Madamanchi; Cam Patterson; Marschall S. Runge

From the Carolina Cardiovascular Biology Center, Department of Medicine, University of North Carolina, Chapel Hill.

Correspondence to Marschall S. Runge, MD PhD, Chairman, Department of Medicine, University of North Carolina at Chapel Hill, 3033 Old Clinic Building, Campus Box 7075, Chapel Hill, NC 27599 to 7005. E-mail mrunge@med.unc.edu

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

The widespread use of nucleoside analog reverse transcriptase inhibitors (NRTIs) and HIV protease inhibitors (PIs) in Western countries has substantially reduced morbidity and mortality in patients with HIV infection. Concomitantly, however, adverse effects associated with long-term use of these agents are becoming recognized. A growing body of literature suggests that many adverse effects associated with the use of NRTIs such as lactic acidosis, hepatic steatosis, myopathy, cardiomyopathy, peripheral neuropathy, pancreatitis and lipodystrophy syndrome are due to mitochondrial toxicity.^1–4 In contrast, the adverse effects associated with the use of PIs, hyperlipidemia, lipodystrophy,⁵ and perhaps, the resulting accelerated atherosclerosis,^6,7 have not been attributed to mitochondrial toxicity. In the October 2002 issue of Atherosclerosis, Thrombosis and Vascular Biology, Zhong et al⁸ challenge this paradigm by demonstrating PI-mediated mitochondrial dysfunction in endothelial cells and the resultant apoptosis-independent cytotoxicity and suggest that PI-induced endothelial cell toxicity contributes to accelerated atherosclerosis in HIV patients.

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Lipoprotein oxidation is a critical step in the initiation of atherosclerosis.⁹ Lipoproteins undergo oxidation by endothelial cells during transport from the plasma into the arterial wall.¹⁰ A clear association has been established between elevated serum LDL cholesterol levels and increased atherosclerotic disease.¹¹ In addition, the extent of oxidation of LDL cholesterol impacts its atherogenic potency.¹² Reduction of LDL cholesterol by diet, exercise,¹³ and/or pharmacologic agents reduces atherosclerotic risk.¹⁴ These data suggest that the accelerated atherosclerosis in HIV patients treated with PIs is due to the PI-induced hyperlipidemia.

Mechanisms of Lipodystrophy and Hyperlipidemia Associated With PIs

Lipodystrophy and hyperlipidemia can occur under conditions that affect mitochondrial integrity . . . [Full Text of this Article]

This article has been cited by other articles:

				N. R. Madamanchi and M. S. Runge Mitochondrial Dysfunction in Atherosclerosis Circ. Res., March 2, 2007; 100(4): 460 - 473. [Abstract] [Full Text] [PDF]