Abstract
Objective: VEGFA isoforms 165a and 165b are pro and antiangiogenic, respectively. We aimed to evaluate the effects of IMM and EDAS in the VEGFA165a/b ratio in patients with ICAS. Methods: This is a prospective observational study of VEGFA165a and b in patients with stenosis greater than 70% due to ICAS. All patients received IMM. Patients with persistent symptoms underwent EDAS while maintaining IMM. Serum samples were collected at baseline, 1 week, 1, 3, and 6 months. VEGFA isoforms were quantified using multiplex sandwich ELISA. All samples were run in duplicate and accepted as valid if the intersample variability was less than 20%. A mixed model was built for the outcome variable VEGFA165a/b ratio using the predictor variables timepoint, treatment, and the interaction of time and treatment. The restricted maximum likelihood method was used to fit the model with random effects to account for the repeated measurements and intersubject variability. Results: A total of 72 patients were enrolled, of which 58 had IMM alone and 14 had EDAS. Mean age was 61.8 ± 12.3, 53% were females. The regression model demonstrated that there were no significant differences in the VEGFA165a/b ratio at baseline and 1 month after enrollment. Significant differences in VEGFA165a/b ratio were found at one week with higher levels in the surgical group (EDAS: 0.46 ± 0.22, IMM: 0.24 ± 0.07, p=0.03) and at 3 and 6 months with higher levels in the IMM group (3m: EDAS: 0.29 ± 0.14, IMM: 0.45 ± 0.20, p=0.03, 6m: EDAS:0.19 ± 0.11, IMM 0.37 ± 0.19 p=0.01). Conclusion: While the surgical event may well explain the early elevation of the VEGFA165a/b ratio one week after surgery, the elevation of a proangiogenic profile by the 3rd and 6th month in the IMM group is relevant. None of the patients in the IMM or EDAS groups had strokes at the last 6 months follow-up, and the peak (early for EDAS and at 3 and 6 months for IMM) of the VEGFA165a/b ratio may indicate a protective effect, averting stroke.
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