ABSTRACT
Increasing evidence suggests that atherosclerosis is an inflammatory disease. Since HIVinfected individuals often develop opportunistic infections and immune activation, the resulting inflammatory response could be an important factor contributing to an accelerated form of atherosclerosis. The mechanism whereby inflammation in HIV infection contributes to atherosclerosis is not fully understood. HIV-infected individuals show evidence of increased nitric oxide (NO) production, suggesting that NO-dependent mechanisms may regulate vascular inflammatory responses. For example, peroxynitrite, a highly reactive chemical species formed from the generation of NO and superoxide radicals, is known to convert low-density lipoprotein (LDL) to an atherogenic oxLDL form, which can then induce endothelial activation. In the case of cocaine, a common drug of abuse, the elaboration of catecholamines may further contribute to endothelial injury and atherosclerosis. We believe the response to cocaine may be mediated partially by effects of catecholamines on the generation of NO. There is evidence suggesting that human atherosclerotic plaques contain the inducible form of nitric oxide synthase (iNOS), which produces NO. Preliminary studies from our laboratory have shown that catecholamines can increase the production of NO in lipopolysaccharide (LPS)-
stimulated macrophages by promoting the expression of iNOS. Although speculative, these data provide a potential link between cocaine abuse in HIV-infected individuals and accelerated atherosclerosis.
