Abstract Body: Pial collateral vessels are small arterial branches connecting the major cerebral arteries, which help reroute cerebral blood flow in the event of large vessel occlusion. Patients with good pial collateral function recover better than those with poor function; however, the underlying etiology for this difference remains unknown. Pre-clinical rodent studies have identified angiopoietins, their subvariants, and receptor Tie2 in regulating collateral function and vascular remodeling following ischemic stroke. Currently, there are no safe and effective therapies to support tissue stability, recovery, or target collateral vessels in ischemic stroke patients. This study seeks to expand the current understanding of pial collateral plasticity by correlating cerebrovascular biomarker levels of Soluble Tie2, Angiopoietin-1 (Ang1), Angiopoietin-2 (Ang2) to collateral function in human patients with acute ischemic stroke. This prospective pilot study included whole blood collection at 3 time points from stroke patients (n=15) undergoing a mechanical thrombectomy. Protein expression was quantified via enzyme-linked immunosorbent assays (ELISA) and compared to matched healthy control serum. Standard-of-care imaging was analyzed to grade participants’ collateral function, and medical charts were reviewed to monitor long-term clinical recovery status. Linear mixed-effect models were conducted to compare biomarker activity levels across the 3 time points. Subjects with higher collateral function are associated with decreased levels of Ang1 and, conversely, elevated concentrations of Ang2 and soluble Tie2. Our findings suggest that greater pial collateral function correlates with alterations in Tie2/angiopoietin signaling due to large vessel occlusion stroke in humans.