[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.