Matrix metalloproteinase dysregulation in HIV infection: implications for therapeutic strategies.
The emerging role of immune activation and inflammation in the pathogenesis of human immunodeficiency virus (HIV) disease has stimulated the search for new approaches for managing HIV infection. Recent evidence suggests that an imbalance between matrix metalloproteinases (MMPs) and endogenous tissue inhibitors of MMPs (TIMPs) might contribute to HIV-associated pathology by inducing remodelling of the extracellular matrix. Here, we discuss the evidence and the potential mechanisms for altered MMP or TIMP function in HIV infection and disease. Furthermore, we outline the possible medical implications for the use of compounds that target MMP activity, and we propose that antiretroviral drugs, particularly HIV protease inhibitors (PIs), and compounds with anti-inflammatory properties, such as statins, natural omega-3 fatty acids and tetracyclines, which inhibit MMP function, might represent useful therapeutic approaches to mitigate potential MMP-related damage during HIV infection.
Mastroianni
Claudio M
CM
Department of Infectious and Tropical Diseases, Sapienza University of Rome, Ospedale S. Maria Goretti, 04100 Latina, Italy. claudio.mastroianni@uniroma1.it
Liuzzi
Grazia M
GM
D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use; D015658:HIV Infections / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D017320:HIV Protease Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D008954:Models, Biological; D015398:Signal Transduction / Q000187:drug effects; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases