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Inflammatory neointima formation: Is leukocyte‐derived myeloperoxidase a key mediator?
Author(s) -
Zhang Chunxiang,
Yang Jiang,
Ji Ruirui
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1454
Subject(s) - mediator , myeloperoxidase , neointima , key (lock) , inflammation , chemistry , microbiology and biotechnology , immunology , medicine , biology , ecology , restenosis , stent
Although a large body of data suggests the involvement of inflammation in atherosclerosis and restenosis, the molecular mechanisms remain unclear due to the lack of direct evident of inflammatory neointima formation. Herein, we infused leukocyte‐derived myeloperoxidase (MPO)(40–200 nM) via rat external carotid artery into the temporarily isolated common carotid artery and incubated for 1 h. The rats were sacrificed at 7, 14 or 28 days after treatment for histology analysis. We found that MPO itself did not induce any neointima formation. However, in the presence of its substrate hydrogen peroxide (H2O2), MPO was able to elicit neointimal hyperplasia. H2O2 itself at our experimental concentrations failed to induce neointima formation. We demonstrated that MPO‐induced neointimal hyperplasia was hypochlorous acid (HOCl), a physiological product of MPO and H2O2, dependent, because the neointima formation was inhibited by HOCl scavenger, L‐methionine and MPO inhibitors. To further confirm our hypothesis, we infused HOCl into the temporarily isolated common carotid artery for 1 h incubation and found that HOCl, at pathophysiology‐related concentrations (0.5–5 mM), elicited neointimal hyperplasia in a time‐ and dose‐dependent manner. To characterize the cytological features a panel of immunohistological markers was used. These immonocytological markers revealed a heterogeneous cell population within MPO and HOCl‐induced neointimal lesions, which included endothelial cells, vascular smooth muscle cells and leukocytes. To our knowledge, MPO and HOCl‐elicited neointimal hyperplasia is a novel inflammatory neointima formation model. As leukocyte‐derived MPO is highly expressed in atherosclerotic and restenotic lesions, it may be a key mediator in these proliferative vascular diseases