Advertisement

Journal of NeuroVirology

, Volume 17, Issue 2, pp 153–158 | Cite as

Marked relationship between matrix metalloproteinase 7 and brain atrophy in HIV infection

  • Ann B. RaginEmail author
  • Ying Wu
  • Renee Ochs
  • Hongyan Du
  • Leon G. Epstein
  • Katherine Conant
  • Justin C. McArthur
Article

Abstract

Circulating levels of matrix metalloproteinases (MMP-1 and 7) have been found to correlate with the severity of brain injury in HIV-infected subjects. This study used high-resolution neuroanatomic imaging and automated segmentation algorithms to clarify this relationship. Both metalloproteinases were significantly correlated with increased cerebrospinal fluid volume fraction. Comprehensive brain volumetric analysis revealed a more marked relationship with atrophy for MMP-7, which was significantly correlated with neural injury in multiple brain regions and nearly all ventricular measurements. MMP-7 was also correlated with measures of virologic and cognitive status.

Keywords

HIV-dementia MMP-1 MMP-7 NeuroAIDS Quantitative MRI 

Notes

Acknowledgements

This work was supported by National Institutes of Health grants: MH66705 (ABR), MH080636 (ABR), NS052580 (KC), and MH075673 (JCM). The NEAD cohort was supported by NS044807 (JCM) and NS049465 (JCM). The authors thank Linda Reisberg, Pippa Storey, and the NEAD consortium.

Declarations

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this paper.

References

  1. Antinori A, Arendt G, Becker JT, Brew BJ, Byrd DA, Cherner M, Clifford DB, Cinque P, Epstein LG, Goodkin K, Gisslen M, Grant I, Heaton RK, Joseph J, Marder K, Marra CM, McArthur JC, Nunn M, Price RW, Pulliam L, Robertson KR, Sacktor N, Valcour V, Wojna VE (2007) Updated research nosology for HIV-associated neurocognitive disorders. Neurology 69:1789–1799PubMedCrossRefGoogle Scholar
  2. Avison MJ, Nath A, Greene-Avison R, Schmitt FA, Bales RA, Ethisham A, Greenberg RN, Berger JR (2004a) Inflammatory changes and breakdown of microvascular integrity in early human immunodeficiency virus dementia. J Neurovirol 10:223–232PubMedCrossRefGoogle Scholar
  3. Avison MJ, Nath A, Greene-Avison R, Schmitt FA, Greenberg RN, Berger JR (2004b) Neuroimaging correlates of HIV-associated BBB compromise. J Neuroimmunol 157:140–146PubMedCrossRefGoogle Scholar
  4. Ban CR, Twigg SM, Franjic B, Brooks BA, Celermajer D, Yue DK, McLennan SV (2010) Serum MMP-7 is increased in diabetic renal disease and diabetic diastolic dysfunction. Diab Res Clin Pract 87:335–341CrossRefGoogle Scholar
  5. Bilousova TV, Rusakov DA, Ethell DW, Ethell IM (2006) Matrix metalloproteinase-7 disrupts dendritic spines in hippocampal neurons through NMDA receptor activation. J Neurochem 97:44–56PubMedCrossRefGoogle Scholar
  6. Bozzo C, Bellomo G, Silengo L, Tarone G, Altruda F (1997) Soluble integrin ligands and growth factors independently rescue neuroblastoma cells from apoptosis under nonadherent conditions. Exp Cell Res 237:326–337PubMedCrossRefGoogle Scholar
  7. Buhler LA, Samara R, Guzman E, Wilson CL, Krizanac-Bengez L, Janigro D, Ethell DW (2009) Matrix metalloproteinase-7 facilitates immune access to the CNS in experimental autoimmune encephalomyelitis. BMC Neurosci 10:17PubMedCrossRefGoogle Scholar
  8. Busiek DF, Baragi V, Nehring LC, Parks WC, Welgus HG (1995) Matrilysin expression by human mononuclear phagocytes and its regulation by cytokines and hormones. J Immunol 154:6484–6491PubMedGoogle Scholar
  9. Chang L, Ernst T, St Hillaire C, Conant K (2004) Antiretroviral treatment alters relationship between MCP-1 and neurometabolites in HIV patients. Antivir Ther 9:431–440PubMedGoogle Scholar
  10. Cinque P, Vago L, Mengozzi M, Torri V, Ceresa D, Vicenzi E, Transidico P, Vagani A, Sozzani S, Mantovani A, Lazzarin A, Poli G (1998) Elevated cerebrospinal fluid levels of monocyte chemotactic protein-1 correlate with HIV-1 encephalitis and local viral replication. AIDS 12:1327–1332PubMedCrossRefGoogle Scholar
  11. Conant K, McArthur JC, Griffin DE, Sjulson L, Wahl LM, Irani DN (1999) Cerebrospinal fluid levels of MMP-2, 7, and 9 are elevated in association with human immunodeficiency virus dementia. Ann Neurol 46:391–398PubMedCrossRefGoogle Scholar
  12. Conant K, St Hillaire C, Nagase H, Visse R, Gary D, Haughey N, Anderson C, Turchan J, Nath A (2004) Matrix metalloproteinase 1 interacts with neuronal integrins and stimulates dephosphorylation of Akt. J Biol Chem 279:8056–8062PubMedCrossRefGoogle Scholar
  13. Dhar A, Gardner J, Borgmann K, Wu L, Ghorpade A (2006) Novel role of TGF-beta in differential astrocyte-TIMP-1 regulation: implications for HIV-1-dementia and neuroinflammation. J Neurosci Res 83:1271–1280PubMedCrossRefGoogle Scholar
  14. Fischl B, Salat DH, Busa E, Albert M, Dieterich M, Haselgrove C, van der Kouwe A, Killiany R, Kennedy D, Klaveness S, Montillo A, Makris N, Rosen B, Dale AM (2002) Whole brain segmentation: automated labeling of neuroanatomical structures in the human brain. Neuron 33:341–355PubMedCrossRefGoogle Scholar
  15. Gartner S (2000) HIV infection and dementia. Science 287:602–604PubMedCrossRefGoogle Scholar
  16. Gu Z, Kaul M, Yan B, Kridel SJ, Cui J, Strongin A, Smith JW, Liddington RC, Lipton SA (2002) S-nitrosylation of matrix metalloproteinases: signaling pathway to neuronal cell death. Science 297:1186–1190PubMedCrossRefGoogle Scholar
  17. Haro H, Crawford HC, Fingleton B, Shinomiya K, Spengler DM, Matrisian LM (2000) Matrix metalloproteinase-7-dependent release of tumor necrosis factor-alpha in a model of herniated disc resorption. J Clin Invest 105:143–150PubMedCrossRefGoogle Scholar
  18. Hwang IK, Park SM, Kim SY, Lee ST (2004) A proteomic approach to identify substrates of matrix metalloproteinase-14 in human plasma. Biochim Biophys Acta 1702:79–87PubMedGoogle Scholar
  19. Johnston JB, Zhang K, Silva C, Shalinsky DR, Conant K, Ni W, Corbett D, Yong VW, Power C (2001) HIV-1 Tat neurotoxicity is prevented by matrix metalloproteinase inhibitors. Ann Neurol 49:230–241PubMedCrossRefGoogle Scholar
  20. Kelder W, McArthur JC, Nance-Sproson T, McClernon D, Griffin DE (1998) Beta-chemokines MCP-1 and RANTES are selectively increased in cerebrospinal fluid of patients with human immunodeficiency virus-associated dementia. Ann Neurol 44:831–835PubMedCrossRefGoogle Scholar
  21. Langford D, Masliah E (2001) Crosstalk between components of the blood brain barrier and cells of the CNS in microglial activation in AIDS. Brain Pathol 11:306–312PubMedCrossRefGoogle Scholar
  22. Lugli E, Pinti M, Nasi M, Troiano L, Prada N, Mussini C, Borghi V, Esposito R, Cossarizza A (2005) MMP-7 promoter polymorphisms do not influence CD4+ recovery and changes in plasma viral load during antiretroviral therapy for HIV-1 infection. Int J Immunogenet 32:269–271PubMedCrossRefGoogle Scholar
  23. McQuibban GA, Gong JH, Wong JP, Wallace JL, Clark-Lewis I, Overall CM (2002) Matrix metalloproteinase processing of monocyte chemoattractant proteins generates CC chemokine receptor antagonists with anti-inflammatory properties in vivo. Blood 100:1160–1167PubMedGoogle Scholar
  24. Milward EA, Fitzsimmons C, Szklarczyk A, Conant K (2007) The matrix metalloproteinases and CNS plasticity: an overview. J Neuroimmunol 187:9–19PubMedCrossRefGoogle Scholar
  25. Nilsson L, Jonasson L, Nijm J, Hamsten A, Eriksson P (2006) Increased plasma concentration of matrix metalloproteinase-7 in patients with coronary artery disease. Clin Chem 52:1522–1527PubMedCrossRefGoogle Scholar
  26. Parks WC, Wilson CL, Lopez-Boado YS (2004) Matrix metalloproteinases as modulators of inflammation and innate immunity. Nat Rev Immunol 4:617–629PubMedCrossRefGoogle Scholar
  27. Patton BL, Chiu AY, Sanes JR (1998) Synaptic laminin prevents glial entry into the synaptic cleft. Nature 393:698–701PubMedCrossRefGoogle Scholar
  28. Persidsky Y, Ghorpade A, Rasmussen J, Limoges J, Liu XJ, Stins M, Fiala M, Way D, Kim KS, Witte MH, Weinand M, Carhart L, Gendelman HE (1999) Microglial and astrocyte chemokines regulate monocyte migration through the blood-brain barrier in human immunodeficiency virus-1 encephalitis. Am J Pathol 155:1599–1611PubMedCrossRefGoogle Scholar
  29. Persidsky Y, Zheng J, Miller D, Gendelman HE (2000) Mononuclear phagocytes mediate blood-brain barrier compromise and neuronal injury during HIV-1-associated dementia. J Leukoc Biol 68:413–422PubMedGoogle Scholar
  30. Powell WC, Fingleton B, Wilson CL, Boothby M, Matrisian LM (1999) The metalloproteinase matrilysin proteolytically generates active soluble Fas ligand and potentiates epithelial cell apoptosis. Curr Biol 9:1441–1447PubMedCrossRefGoogle Scholar
  31. Pulliam L, Gascon R, Stubblebine M, McGuire D, McGrath MS (1997) Unique monocyte subset in patients with AIDS dementia. Lancet 349:692–695PubMedCrossRefGoogle Scholar
  32. Ragin AB, Wu Y, Ochs R, Scheidegger R, Cohen BA, McArthur JC, Epstein LG, Conant K (2009) Serum matrix metalloproteinase levels correlate with brain injury in human immunodeficiency virus infection. J Neurovirol: 1-7Google Scholar
  33. Rumbaugh J, Turchan-Cholewo J, Galey D, St Hillaire C, Anderson C, Conant K, Nath A (2006) Interaction of HIV Tat and matrix metalloproteinase in HIV neuropathogenesis: a new host defense mechanism. FASEB J 20:1736–1738PubMedCrossRefGoogle Scholar
  34. Sasseville VG, Newman W, Brodie SJ, Hesterberg P, Pauley D, Ringler DJ (1994) Monocyte adhesion to endothelium in simian immunodeficiency virus-induced AIDS encephalitis is mediated by vascular cell adhesion molecule-1/alpha 4 beta 1 integrin interactions. Am J Pathol 144:27–40PubMedGoogle Scholar
  35. Schlondorff J, Blobel CP (1999) Metalloprotease-disintegrins: modular proteins capable of promoting cell-cell interactions and triggering signals by protein-ectodomain shedding. J Cell Sci 112(Pt 21):3603–3617PubMedGoogle Scholar
  36. Sevigny JJ, Albert SM, McDermott MP, McArthur JC, Sacktor N, Conant K, Schifitto G, Selnes OA, Stern Y, McClernon DR, Palumbo D, Kieburtz K, Riggs G, Cohen B, Epstein LG, Marder K (2004) Evaluation of HIV RNA and markers of immune activation as predictors of HIV-associated dementia. Neurology 63:2084–2090PubMedGoogle Scholar
  37. Sternlicht MD, Werb Z (2001) How matrix metalloproteinases regulate cell behavior. Annu Rev Cell Dev Biol 17:463–516PubMedCrossRefGoogle Scholar
  38. Suryadevara R, Holter S, Borgmann K, Persidsky R, Labenz-Zink C, Persidsky Y, Gendelman HE, Wu L, Ghorpade A (2003) Regulation of tissue inhibitor of metalloproteinase-1 by astrocytes: links to HIV-1 dementia. Glia 44:47–56PubMedCrossRefGoogle Scholar
  39. Thompson PM, Dutton RA, Hayashi KM, Toga AW, Lopez OL, Aizenstein HJ, Becker JT (2005) Thinning of the cerebral cortex visualized in HIV/AIDS reflects CD4+ T lymphocyte decline. Proc Natl Acad Sci USA 102:15647–15652PubMedCrossRefGoogle Scholar
  40. Towfighi A, Skolasky RL, St Hillaire C, Conant K, McArthur JC (2004) CSF soluble Fas correlates with the severity of HIV-associated dementia. Neurology 62:654–656PubMedGoogle Scholar
  41. Valcour VG, Shikuma CM, Watters MR, Sacktor NC (2004) Cognitive impairment in older HIV-1-seropositive individuals: prevalence and potential mechanisms. AIDS 18(Suppl 1):S79–S86PubMedGoogle Scholar
  42. Van Lint P, Libert C (2007) Chemokine and cytokine processing by matrix metalloproteinases and its effect on leukocyte migration and inflammation. J Leukoc Biol 82:1375–1381PubMedCrossRefGoogle Scholar
  43. Vos CM, Sjulson L, Nath A, McArthur JC, Pardo CA, Rothstein J, Conant K (2000) Cytotoxicity by matrix metalloprotease-1 in organotypic spinal cord and dissociated neuronal cultures. Exp Neurol 163:324–330PubMedCrossRefGoogle Scholar
  44. Weiss JM, Nath A, Major EO, Berman JW (1999) HIV-1 tat induces monocyte chemoattractant protein-1-mediated monocyte transmigration across a model of the human blood-brain barrier and up-regulates CCR5 expression on human monocytes. J Immunol 163:2953–2959PubMedGoogle Scholar
  45. Yu WH, Woessner JF Jr (2000) Heparan sulfate proteoglycans as extracellular docking molecules for matrilysin (matrix metalloproteinase 7). J Biol Chem 275:4183–4191PubMedCrossRefGoogle Scholar
  46. Zhang K, McQuibban GA, Silva C, Butler GS, Johnston JB, Holden J, Clark-Lewis I, Overall CM, Power C (2003a) HIV-induced metalloproteinase processing of the chemokine stromal cell derived factor-1 causes neurodegeneration. Nat Neurosci 6:1064–1071CrossRefGoogle Scholar
  47. Zhang KMG, Silva C, Butler GS, Johnston JB, Holden J, Clark-Lewis I, Overall CM, Power C (2003b) HIV-induced metalloproteinase cleavage of the chemokine SDF-1alpha causes neurodegeneration. Nat Neurosci 6:1064–1011CrossRefGoogle Scholar

Copyright information

© Journal of NeuroVirology, Inc. 2011

Authors and Affiliations

  • Ann B. Ragin
    • 1
    Email author
  • Ying Wu
    • 2
  • Renee Ochs
    • 1
  • Hongyan Du
    • 3
  • Leon G. Epstein
    • 4
  • Katherine Conant
    • 5
  • Justin C. McArthur
    • 6
  1. 1.Department of RadiologyNorthwestern UniversityChicagoUSA
  2. 2.Ctr. for Advanced ImagingNorth Shore University HospitalEvanstonUSA
  3. 3.Ctr. for Clinical Research InformaticsNorth Shore University HospitalEvanstonUSA
  4. 4.Division of NeurologyChildren’s Memorial HospitalChicagoUSA
  5. 5.Department of NeuroscienceGeorgetown University Medical CtrWashingtonUSA
  6. 6.Department of NeurologyJohns Hopkins UniversityBaltimoreUSA

Personalised recommendations