Abstract W MP35: Localized Increase of Myeloperoxidase in the Lumen of Human Cerebral Aneurysms
The neutrophil granule protein myeloperoxidase (MPO) reacts with H2O2 to oxidize chloride, thereby generating hypochlorous acid (HOCl), a highly reactive product. Circulating levels of MPO are increased in many inflammatory diseases, and have been linked to oxidative stress and elevated risk for vascular disease in humans. We hypothesized that MPO is increased locally in human intracranial aneurysms. Blood, both from the lumen of the aneurysm and femoral artery, and tissue, both from the aneurysm wall and from a superficial temporal artery, were sampled from seventeen patients with intracranial aneurysms who underwent microsurgical clipping. Plasma concentrations of MPO (ELISA) were 3-fold higher in aneurysm (100±15 ng/ml) (mean±SE) than in femoral blood (33±10; p=0.0007). Plasma concentrations of vascular peroxidase 1 (VPO1), a homologue of MPO that is expressed in endothelial cells, were not increased in aneurysm (384±51 μg/ml) compared to femoral blood (513±65; p=0.12). mRNA expression (RT-qPCR) was similar in leukocytes recovered from aneurysmal blood (2005±377 copies/50 ng RNA for MPO and 342±98 for VPO1) and femoral blood (2129±313 for MPO and 381±61 for VPO1; p=0.5 and 0.73, respectively). There were significantly more MPO-positive cells (immunohistochemistry) in aneurysm tissue (69±8 positive cells/field, 32%±3% of total cells) than superficial temporal artery (6±3 positive cells/field, 2%±1%; p<0.001). These findings suggest that MPO is increased specifically and locally in aneurysm blood and tissue, and the increase is contributed by MPO-positive cells in aneurysm tissue. We speculate that local MPO may contribute to the formation and/or rupture of intracranial aneurysms, and thus, could be a therapeutic target.
Author Disclosures: D.M. Hasan: None. Y. Chu: None. W.M. Nauseef: None. G.L. Pierce: None. G. Cheng: None. L. Wegman-Points: None. R.A. Pena Silva: None. D.D. Heistad: None.
- © 2014 by American Heart Association, Inc.