Myeloperoxidase in Human Intracranial Aneurysms

Abstract

Background and Purpose Non-invasive imaging identifying a predictive biomarker of the bleeding risk of unruptured intracranial aneurysms (UIA) is needed. We investigated a potential biomarker of UIA instability, myeloperoxidase (MPO), in human aneurysm tissue. Methods Human brain aneurysms were harvested following clipping, and histologically and biochemically evaluated for the presence of MPO. Of the tissue collected, 3 were from ruptured aneurysms and 20 were from UIAs. For each UIA, its 5-year aneurysm rupture risk (ARR) was determined using the PHASES model. Results All ruptured aneurysms were MPO-positive. Of the UIAs, half were MPO-positive. The median 5-year ARR was higher for MPO-positive UIA (2.28%) than MPO-negative UIA (0.69%) and the distributions were statistically different (p<0.005, Wilcoxon-Mann-Whitney test). The likelihood for MPO-positive UIA was significantly associated (p=0.031) with ARR (Odds Ratio: 4.79; 95% confidence limits: 1.15–19.96). Conclusion MPO is associated with PHASES estimated risk of aneurysm rupture and may potentially be used as an imaging biomarker of aneurysm instability.

Search for Biomarkers of Intracranial Aneurysms: A Systematic Review

“…It comes as no surprise then that we see positive MPO in RA tissue as well as in UA tissue in patients with a higher predicted rupture risk. MPO is an enzyme secreted in the phagolysosomes of neutrophils and it is believed the reactive oxygen species generated by MPO in the respiratory burst add to vessel wall damage (11). Consistent with these findings we also see increased levels of proinflammatory cytokines related to monocytes and neutrophils in IA, particularly GM-CSF, IL-1β, MCP-1, and TNF-α.…”

“…Moreover, M1 macrophages and mast cell expression were significantly higher in ruptured than unruptured aneurysms. Myeloperoxidase (MPO) was found in all 3 samples of RA tissue and 10 out of 20 samples of UA tissue in one study (11). MPO positive UA tissue was also associated with an increased risk of rupture.…”

MR Imaging of Myeloperoxidase Activity in a Model of the Inflamed Aneurysm Wall

“…More recently, MPO presence has been correlated with the PHASES model of the annual rupture risk of aneurysms. 10 In addition to its role in inflammation, MPO mediates oxidative cell stress due to the production of reactive oxygen species contributing to vessel wall damage. Building on previous work with human aneurysm tissue 32, 33 a rat model was developed where an allogeneic arterial graft was decelluarized prior to its anastomosis to the aorta of the experimental animal.…”

“…Recently, MPO presence in human brain aneurysm specimens was shown to correlate with the PHASES model 9 of aneurysm risk of rupture. 10 Enzymatic activity of neutrophilic myeloperoxidase can be used as a highly selective and sensitive target for detecting inflammation using clinical imaging modalities (MRI, SPECT) 11-15 . Gadolinium(III)-chelate MPO activity-sensing MR imaging probe has also been investigated in an animal model of inflamed saccular aneurysms.…”

Inflammation in human cerebral aneurysms: pathogenesis, diagnostic imaging, genetics, and therapeutics

“…[55] Previously, Deleo et al [56] developed a method to access MPO enzymatic activity as an inflammatory biomarker in a rabbit model of IA. The group used clinical field strength MRI and an MPO specific paramagnetic substrate, di-5-hydroxytryptamide of gadopentetate dimeglumine, as an MR contrast agent.…”