Introduction: Abundant preclinical studies show efficacy for therapies targeted to the protective axis of the renin-angiotensin system in stroke. The expression and activity of angiotensin converting enzyme 2 (ACE2), a cardio and neuro-protective carboxypeptidase in this axis, have recently been shown to be dynamically altered during stroke in animal models.
Hypothesis: The aim of this study was to characterize the previously unexplored changes in activity of ACE2, and other RAS enzymes, in the serum of patients experiencing acute ischemic stroke.
Methods: Blood samples were obtained from patients with acute ischemic stroke (n=20) at presentation and again at three days post-stroke and enzyme activity levels in isolated serum were analyzed by fluorometric assay. These were compared to enzyme activity levels in samples obtained from a cohort of patients presenting with transient ischemic attack or other clinical presentations mimicking stroke and from healthy control participants (n=20).
Results: Ischemic stroke resulted in significantly lower levels of serum ACE2 activity at an average of 3.5 hours after stroke as compared to both transient ischemic attack/stroke mimic and healthy control participant levels, followed three days later by an increase back to control levels. ACE activity was also significantly decreased following stroke, but without increases at three days. Renin enzyme activity during stroke did not significantly differ from controls at either time point. Serum ACE2 activity was negatively correlated with systolic blood pressure at presentation among stroke patients, while activity levels from a separate cohort of healthy young adults were positively correlated. Multiple regression analyses indicated that ACE2 activity levels were significantly correlated with a diagnosis of ischemic stroke, with those in the lowest tertile of all participants were at 7.7 times increased odds of having had a stroke.
Conclusions: The characterization of the dynamic and novel changes in serum ACE2 activity in human stroke, which concur with preclinical studies, along with the demonstration of correlations with systolic blood pressure, provides new insight for the development of therapies that target this protective system in ischemic stroke.