Myoglobin in cerebral aneurysm walls: Potential origin from smooth muscle-derived myofibroblasts and role in collagen retention

The mechanisms underlying cerebral aneurysm wall fragility remain unclear. Proteomic analysis has revealed predominant expression of myoglobin in thickened aneurysm wall regions. Given its nitric oxide-scavenging function, myoglobin may enhance wall stability. Hence, we aimed to elucidate its biological relevance in aneurysm wall specimens collected during surgical clipping. Immunostaining confirmed the presence of myoglobin and α-smooth muscle actin (α-SMA) in all 21 specimens. Double-immunofluorescence staining demonstrated that myoglobin was primarily localized on the luminal side of the α-SMA-positive layer. The median colocalization rates were 19.7% (interquartile range [IQR], 7.2%-43.4%) in the α-SMA-positive areas and 24.7% (IQR, 10.9%-56.8%) in the α-SMA-positive cells. Periostin staining demonstrated partial colocalization with α-SMA within the smooth muscle layer, with additional periostin-positive cells located luminally, beyond α-SMA expression. The colocalization rates of periostin were 41.8 ± 25.0% in α-SMA-positive areas and 55.8 ± 25.2% in α-SMA-positive cells. Myoglobin and periostin were highly expressed on the luminal sides, with median colocalization rates of 96.4% (IQR, 72.3%-99.0%) and 97.1% (IQR, 87.0%-100%) in periostin-positive areas/cells. Myoglobin density was positively correlated with collagen content. These findings suggest that periostin-expressing migrated myofibroblasts may produce myoglobin that could enhance collagen retention, wall thickening, and cerebral aneurysm wall stability.