Matrix metalloproteinases and vascular endothelial growth factor in the acute phase of ischemic stroke: correlation with pathogenetic subtypes and clinical outcomes

Objective. To evaluate the changes in serum levels of matrix metalloproteinase (MMP)-2, MMP-9, and vascular endothelial growth factor (VEGF) during the acute phase of ischemic stroke (IS) to elucidate subtype-specific pathogenetic mechanisms and assess the predictive value of these biomarkers for clinical and functional recovery in patients. Material and methods. The study included 114 patients diagnosed with IS. Participants were categorized into the following groups: Group 1 (n=26) with atherothrombotic stroke, Group 2 (n=29) with cardioembolic stroke, and Group 3 (n=59) with lacunar stroke or unspecified etiology. A comparison group included 13 healthy subjects. The observation period extended over 14 days, with assessments conducted at two time points: I — 48—72 hours post-onset of symptoms and II — Day 14. The clinical evaluation utilized the Glasgow Coma Scale (GCS), the National Institutes of Health Stroke Scale (NIHSS), and the Modified Rankin Scale (mRS). Serum levels of MMP-2 and MMP-9 were measured using enzyme-linked immunosorbent assay (ELISA), while VEGF levels were assessed on a multiplex analyzer. Results. The highest severity of neurological deficit was observed in Groups 1 and 2, whereas Group 3 exhibited minimal disorders. Notably, VEGF levels during the initial 48—72 hours were significantly lower in the cardioembolic subtype (p=0.039). In contrast, Group 3 displayed an increase in VEGF by Day 14 (pI—II=0.009), which correlated with improvements in NIHSS and mRS scores (pI—II=<0.001). Correlation analyses indicated subtype-specific relationships: in Group 1, a positive correlation between VEGF at timepoint II and MMP-9 at timepoint I (r=0.898; p=0.002) was associated with less favorable outcomes; in Group 2, a negative correlation between MMP-9 at timepoint I and NIHSS at timepoint I (r=–0.427; p=0.042) was observed; in Group 3, negative correlations between MMP-2 and both NIHSS and mRS were identified (p<0.05). Analysis of risk factors indicated that age negatively correlated with GCS in the atherothrombotic subtype of IS (p<0.05). The «obesity paradox» was evident in the cardioembolic group, revealing a positive correlation between body mass index (BMI) and GCS at timepoint II (p=0.036). Strong correlations were also established between the functional class of coronary heart disease (CHD) and the severity of neurological deficit. Conclusion. This study has elucidated subtype-specific biomarker responses in ischemic stroke: the identified protective role of MMP-2 in lacunar stroke, the paradoxical adaptive features of MMP-9 in the cardioembolic subtype, and the synergistic destructive effects of VEGF and MMP-9 in atherothrombotic subtype.