Abstract 12650: Activity of Serum Angiotensin Converting Enzyme 2 is Decreased During Acute Ischemic Stroke in Humans

Abstract

Introduction: The expression and activity of angiotensin converting enzyme 2 (ACE2), a cardio and neuro-protective carboxypeptidase, has recently been shown to be dynamically altered during and after stroke in animal models. Hypothesis: The aim of this study was to characterize the previously unexplored changes in activity of ACE2 in the serum of patients experiencing acute ischemic stroke. Methods: Serum samples were obtained from patients presenting with acute ischemic stroke (n=20) and again at three days post-stroke and enzyme activity levels were analyzed by fluorometric assay and compared to levels from non-stroke control patients (n=20). Results: Ischemic stroke resulted in a significant decrease in serum ACE2 at an average of 3.5 hours after stroke, which was followed by a rebound increase by three days later (Fig 1). ACE activity was also significantly decreased following stroke, but without rebound increases. Tumor necrosis factor-alpha converting enzyme activity was not significantly different from control. ACE2 activity was negatively correlated with systolic blood pressure (SBP) among stroke patients (Fig 2), while activity was positively correlated with SBP among a cohort of healthy young adults (n=16). Conclusions: The characterization of the dynamic and novel changes in serum ACE2 activity in human stroke, which follow observations from preclinical studies, along with the demonstration of a negative association with SBP, provides new insight for the development of therapies that target this protective system in the context of ischemic stroke. Data are mean ± SEM. RFU: relative fluorescence units; *p<0.001 vs. control; †p<0.05 vs. 4h post stroke.