Expression of matrix metalloproteinase‐9 in mononuclear cells of hyperhomocysteinaemic subjects
- 19 June 2003
- journal article
- research article
- Published by Wiley in European Journal of Clinical Investigation
- Vol. 33 (7), 555-560
- https://doi.org/10.1046/j.1365-2362.2003.01189.x
Abstract
Atherosclerotic plaque instability and rupture requires extracellular matrix modification, a complex process regulated by matrix metalloproteinases (MMPs). We hypothesized that homocysteine's atherogenic effects may involve MMP‐mediated mechanisms. Our results showed the following: (i) Compared with healthy control subjects (n = 9), patients with hyperhomocysteinaemia (n = 9) had elevated mRNA levels of MMP‐9 and tissue inhibitors of metalloproteinases‐1 (TIMP‐1) in freshly isolated peripheral blood mononuclear cells (PBMCs), which were positively correlated with homocysteine and negatively correlated with folate and vitamin B12 levels. (ii) Peripheral blood mononuclear cells obtained from these patients released markedly enhanced the amount of MMP‐9 upon oxidized LDL (oxLDL) stimulation, whereas no such enhancing effect was seen in cells from healthy controls. (iii) During folic acid 6 weeks’ treatment, normalization of homocysteine levels was accompanied by a significant reduction in mRNA levels of MMP‐9 and TIMP‐1 in PBMCs, as well as a marked reduction in oxLDL‐stimulated release of MMP enzyme activity. These novel findings may suggest that homocysteine exerts its atherogenic effect in part by elevating levels and activity of MMPs, which in turn may enhance matrix degradation, potentially promoting atherogenesis and plaque instability. Moreover, our findings suggest that folic acid supplementation may down‐regulate these inappropriate responses in these patients.Keywords
This publication has 23 references indexed in Scilit:
- Folic Acid Treatment Reduces Chemokine Release From Peripheral Blood Mononuclear Cells in Hyperhomocysteinemic SubjectsArteriosclerosis, Thrombosis, and Vascular Biology, 2002
- Inhibition of transcription factor NF-κB reduces matrix metalloproteinase-1, -3 and -9 production by vascular smooth muscle cellsCardiovascular Research, 2001
- Transforming Growth Factor-β- and Tumor Necrosis Factor-α-mediated Induction and Proteolytic Activation of MMP-9 in Human SkinJournal of Biological Chemistry, 2001
- Hyperhomocysteinemia enhances vascular inflammation and accelerates atherosclerosis in a murine modelJournal of Clinical Investigation, 2001
- INTERLEUKIN 15 STIMULATES PRODUCTION OF MATRIX METALLOPROTEINASE-9 AND TISSUE INHIBITOR OF METALLOPROTEINASE-1 BY HUMAN PERIPHERAL BLOOD MONONUCLEAR CELLSCytokine, 2001
- Homocysteine-respondent Genes in Vascular Endothelial Cells Identified by Differential Display AnalysisJournal of Biological Chemistry, 1996
- Matrix Metalloproteinases and Cardiovascular DiseaseCirculation Research, 1995
- A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakesPublished by American Medical Association (AMA) ,1995
- Interstitial Collagenase (MMP-1) Expression in Human Carotid AtherosclerosisCirculation, 1995
- Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques.Journal of Clinical Investigation, 1994