How HIV protease inhibitors promote atherosclerotic lesion formation.
OBJECTIVE
One of the aims of this review is to summarize recent clinical approaches used to determine the role of HIV protease inhibitors in the development of cardiovascular disease. Another aim is to discuss possible molecular mechanisms whereby HIV protease inhibitors may promote atherogenesis.


RESULTS
Several clinical studies have recently used ultrasonography to demonstrate increased intimal medial thickness and alterations in the structural characteristics of epi-aortic lesions in patients receiving HIV protease inhibitors. Molecular studies have indicated that several mechanisms are likely involved in mediating the effects of protease inhibitors. Possible mechanisms include inhibition of the proteasome, increased CD36 expression in macrophage, inhibition of lipoprotein lipase-mediated lipolysis, decreased adiponectin levels, and dysregulation of the NF-kappaB pathway.


CONCLUSIONS
The currently available data strongly suggest that HIV protease inhibitors negatively impact the cardiovascular system. As is often the case with complex diseases like atherosclerosis it appears that HIV protease inhibitors affect the cardiovascular system through several distinct mechanisms by affecting various components of the arterial wall directly or indirectly by influencing lipoprotein and glucose metabolism of the body.
Thomas
Candice M
CM
Department of Pediatrics, University of Kentucky, Lexington, Kentucky 40536-0230, USA.
Smart
Eric J
EJ
D000818:Animals; D050197:Atherosclerosis / Q000139:chemically induced / Q000473:pathology*; D002339:Carotid Arteries / Q000187:drug effects* / Q000473:pathology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D017320:HIV Protease Inhibitors / Q000009:adverse effects*; D006801:Humans; D012307:Risk Factors; D017540:Tunica Media / Q000187:drug effects / Q000473:pathology
D017320:HIV Protease Inhibitors