Molecular mechanisms of HIV protease inhibitor-induced endothelial dysfunction

J Acquir Immune Defic Syndr. 2007 Apr 15;44(5):493-9. doi: 10.1097/QAI.0b013e3180322542.


Highly active antiretroviral therapy incorporating protease inhibitors (PIs) is successful in controlling HIV infection and has dramatically improved the prognosis of HIV-infected patients. The therapeutic benefit of long-term use of HIV PIs is compromised by an increased risk of cardiovascular disease, however, including metabolic syndrome and endothelial dysfunction. Although clinical evidence strongly suggests an association of the use of HIV PIs with endothelial dysfunction, the underlying molecular mechanisms have not been fully elucidated yet. In this review, we describe recent advances in the molecular mechanisms of PI-induced endothelial dysfunction. The available evidence demonstrates that certain HIV PIs could induce endothelial dysfunction, including a decrease of endothelium-dependent vasorelaxation, inhibition of the nitric oxide synthase system, increase of oxidative stress, and activation of mitogen-activated protein kinases. HIV infection itself may also induce endothelial dysfunction and injury. These new discoveries provide a better understanding of the molecular mechanisms of the interaction between HIV PIs and vascular cells and may suggest potential approaches to control HIV PI-associated cardiovascular complications.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Antioxidants / pharmacology
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / physiopathology
  • Gene Expression / drug effects
  • HIV Infections / drug therapy
  • HIV Infections / physiopathology
  • HIV Protease Inhibitors / adverse effects*
  • Humans
  • In Vitro Techniques
  • Nitric Oxide Synthase Type III / genetics
  • Oxidation-Reduction
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Vasodilation / drug effects


  • Antioxidants
  • HIV Protease Inhibitors
  • RNA, Messenger
  • NOS3 protein, human
  • Nitric Oxide Synthase Type III