MMPs/TIMPs imbalances in the peripheral blood and cerebrospinal fluid are associated with the pathogenesis of HIV-1-associated neurocognitive disorders.

HIV-1-associated neurocognitive disorders (HAND) continue to be a major concern in the infected population, despite the widespread use of combined antiretroviral therapy (cART). Growing evidence suggests that an imbalance between matrix metalloproteinases (MMPs) and endogenous tissue inhibitors of MMPs (TIMPs) contributes to the pathogenesis of HAND. In our present study, we examined protein levels and enzymatic activities of MMPs and TIMPs in both plasma and cerebrospinal fluid (CSF) samples from HIV-1 patients with or without HAND and HIV-1-negative controls. Imbalances between MMPs and TIMPs with distinct patterns were revealed in both the peripheral blood and CSF of HIV-1 patients, especially those with HAND. In the peripheral blood, the protein levels of MMP-2, MMP-9, TIMP-1, TIMP-2, and the enzymatic activities of MMP-2 and MMP-9 were increased in HIV-1 patients with or without HAND when compared with HIV-1-negative controls. The enzymatic activity of MMP-2, but not MMP-9, was further increased in plasma samples of HAND patients than that of HIV-1 patients without HAND. Notably, the ratio of MMP-2/TIMP-2 in plasma was significantly increased in HAND patients, not in patients without HAND. In the CSF, MMP-2 activity was increased, but the ratio of MMP-2/TIMP-2 was not altered. De novo induction and activation of MMP-9 in the CSF of HAND patients was particularly prominent. The imbalances between MMPs and TIMPs in the blood and CSF were related to the altered profiles of inflammatory cytokines/chemokines and monocyte activation in these individuals. In addition, plasma from HIV-1 patients directly induced integrity disruption of an in vitro blood-brain barrier (BBB) model, leading to increased BBB permeability and robust transmigration of monocytes/macrophages. These results indicate that imbalances between MMPs and TIMPs are involved in BBB disruption and are implicated in the pathogenesis of neurological disorders such as HAND in HIV-1 patients.

Xing Y ，Shepherd N ，Lan J ，Li W ，Rane S ，Gupta SK ，Zhang S ，Dong J ，Yu Q ... -  《-》

Matrix metalloproteinases and their tissue inhibitors in serum and cerebrospinal fluid of patients with amyotrophic lateral sclerosis.

Niebroj-Dobosz I ，Janik P ，Sokołowska B ，Kwiecinski H ... -  《-》

Matrix metalloproteinases and tissue inhibitors of metalloproteinases in sera and tissue of patients with Dupuytren's disease.

Ulrich D ，Hrynyschyn K ，Pallua N 《PLASTIC AND RECONSTRUCTIVE SURGERY》

Loss of flow induces leukocyte-mediated MMP/TIMP imbalance in dynamic in vitro blood-brain barrier model: role of pro-inflammatory cytokines.

Krizanac-Bengez L ，Hossain M ，Fazio V ，Mayberg M ，Janigro D ... -  《AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY》

Matrix-metalloproteinases and their inhibitors in plasma and tumor tissue of patients with renal cell carcinoma.

Matrix-metalloproteinases (MMPs) are associated with invasive and metastatic behavior of several human malignant tumors. We have determined MMP-2 and MMP-9 and tissue inhibitors of MMPs (TIMP-1 and TIMP-2) in blood plasma and in renal tissue samples of patients with renal cell carcinoma (RCC) from cancerous and non-cancerous parts of the same kidney. In tumor tissue, MMP-9 and TIMP-1 were significantly higher than in normal counterparts. MMP-2 was not different between tumor tissue and normal counterparts. TIMP-2 values could not be measured. In plasma, MMP-9 concentrations were significantly higher in RCC patients than in healthy controls, MMP-2 and TIMP-2 concentrations were higher in healthy controls and TIMP-1 concentrations were not different.

Lein M ，Jung K ，Laube C ，Hübner T ，Winkelmann B ，Stephan C ，Hauptmann S ，Rudolph B ，Schnorr D ，Loening SA ... -  《INTERNATIONAL JOURNAL OF CANCER》