title: Serum activity of angiotensin converting enzyme 2 is decreased in patients with acute ischemic stroke.
abstract: Levels of angiotensin converting enzyme 2 (ACE2), a cardio and neuro-protective carboxypeptidase, are dynamically altered after stroke in preclinical models. We sought to characterize the previously unexplored changes in serum ACE2 activity of stroke patients and the mechanism of these changes. Serum samples were obtained from patients during acute ischemic stroke (n=39), conditions mimicking stroke (stroke-alert, n=23), or from control participants (n=20). Enzyme activity levels were analyzed by fluorometric assay and correlated with clinical variables by regression analyses. Serum ACE2 activity was significantly lower in acute ischemic stroke as compared to both control and stroke-alert patients, followed by an increase to control levels at three days. Serum ACE2 activity significantly correlated with the presence of ischemic stroke after controlling for other factors (P=0.01). Additional associations with ACE2 activity included a positive correlation with systolic blood pressure at presentation in stroke-alert (R(2)=0.24, P=0.03), while stroke levels showed no correlation (R(2)=0.01, P=0.50). ACE2 sheddase activity was unchanged between groups. These dynamic changes in serum ACE2 activity in stroke, which concur with preclinical studies, are not likely to be driven primarily by acute changes in blood pressure or sheddase activity. These findings provide new insight for developing therapies targeting this protective system in ischemic stroke.
authors.affiliation: Department of Physiology and Functional Genomics, University of Florida, USA douglasbennion@gmail.com.
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Bennion
authors.affiliation: Neurovascular Division, Department of Neurology, University of Florida, USA.
authors.forename: Christian A
authors.initials: CA
authors.lastname: Rosado
authors.affiliation: Department of Physiology and Functional Genomics, University of Florida, USA.
authors.forename: Emily A
authors.initials: EA
authors.lastname: Haltigan
authors.affiliation: Department of Physiology and Functional Genomics, University of Florida, USA.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Regenhardt
authors.affiliation: Department of Physiology and Functional Genomics, University of Florida, USA.
authors.forename: Colin
authors.initials: C
authors.lastname: Sumners
authors.affiliation: Neurovascular Division, Department of Neurology, University of Florida, USA.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Waters
mesh_terms: D000085962:Angiotensin-Converting Enzyme 2; D001794:Blood Pressure; D002545:Brain Ischemia / Q000097:blood* / Q000150:complications / Q000201:enzymology* / Q000503:physiopathology; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000097:blood*; D020521:Stroke / Q000097:blood* / Q000150:complications / Q000201:enzymology* / Q000503:physiopathology; D013599:Systole
chemical_list: C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2
keywords: Angiotensin converting enzyme 2 (ACE2); angiotensin converting enzyme (ACE); angiotensin-(1–7); ischemic stroke; renin–angiotensin system