Comparative analysis of matrix metalloproteinases and growth factors in aneurysmal and perimesencephalic subarachnoid hemorrhage: Evidence for an aneurysm-driven molecular response

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) and perimesencephalic subarachnoid hemorrhage (PM-SAH) share similar acute clinical presentations but differ markedly in etiology, vascular pathology, and outcome. The molecular mechanisms underlying these differences remain poorly defined. METHODS: In this prospective observational study, circulating levels of matrix metalloproteinases (MMP-1, MMP-2, MMP-7, MMP-9, MMP-10) and growth factors (EGF, FGF-2, PDGF-AA, PDGF-AB/BB, TGF-α, VEGF-A) were analyzed in patients with aSAH (n = 38) and PM-SAH (n = 40) within 24 h after ictus. Serum biomarker concentrations were quantified and compared between groups, and inter-marker correlations were evaluated. RESULTS: Serum levels of MMP-1, MMP-7, and MMP-9 were significantly higher in the aSAH group than in the PM-SAH group, whereas MMP-2 and MMP-10 showed no significant difference. Among growth factors, EGF, PDGF-AA, PDGF-AB/BB, and VEGF-A were markedly elevated in aSAH, while FGF-2 and TGF-α levels remained comparable across groups. Distinct correlation patterns between MMPs and growth factors were observed in the two cohorts. CONCLUSIONS: The observed biomarker differences between aSAH and PM-SAH likely reflect the presence of an aneurysmal lesion and its associated vascular injury, rather than a generalized response to subarachnoid blood. Elevated MMP and growth factor levels in aSAH point to enhanced extracellular matrix degradation, blood-brain barrier disruption, and a more pronounced aneurysm-associated vascular remodeling and endothelial activation signature, processes not evident in PM-SAH. These findings provide clinical evidence supporting the hypothesis that aneurysm rupture initiates a unique cascade of molecular events contributing to the distinct pathophysiology and poorer outcomes of aSAH.