title: Role of circulating angiotensin converting enzyme 2 in left ventricular remodeling following myocardial infarction: a prospective controlled study.
abstract: Angiotensin-converting enzyme 2 (ACE2) cleaves Angiotensin-II to Angiotensin-(1-7), a cardioprotective peptide. Serum soluble ACE2 (sACE2) activity is raised in chronic heart failure, suggesting a compensatory role in left ventricular dysfunction. Our aim was to study the relationship between sACE2 activity, infarct size, left ventricular systolic function and remodeling following ST-elevation myocardial infarction (STEMI). A contrast-enhanced cardiac magnetic resonance study was performed acutely in 95 patients with first STEMI and repeated at 6 months to measure LV end-diastolic volume index, ejection fraction and infarct size. Baseline sACE2 activities, measured by fluorescent enzymatic assay 24 to 48 hours and at 7 days from admission, were compared to that obtained in 22 matched controls. Patients showed higher sACE2 at baseline than controls (104.4 [87.4-134.8] vs 74.9 [62.8-87.5] RFU/µl/hr, p<0.001). At seven days, sACE2 activity significantly increased from baseline (115.5 [92.9-168.6] RFU/µl/hr, p<0.01). An inverse correlation between sACE2 activity with acute and follow-up ejection fraction was observed (r = -0.519, p<0.001; r = -0.453, p = 0.001, respectively). Additionally, sACE2 directly correlated with infarct size (r = 0.373, p<0.001). Both, infarct size (β = -0.470 [95%CI:-0.691:-0.248], p<0.001) and sACE2 at 7 days (β = -0.025 [95%CI:-0.048:-0.002], p = 0.030) were independent predictors of follow-up ejection fraction. Patients with sACE2 in the upper tertile had a 4.4 fold increase in the incidence of adverse left ventricular remodeling (95% confidence interval: 1.3 to 15.2, p = 0.027). In conclusion, serum sACE2 activity rises in relation to infarct size, left ventricular systolic dysfunction and is associated with the occurrence of left ventricular remodeling.
authors: Thorax Institute, Hospital Clínic, Institut d'investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain. jtortiz@clinic.ub.es
authors: José T
authors: JT
authors: Ortiz-Pérez
authors: Marta
authors: M
authors: Riera
authors: Xavier
authors: X
authors: Bosch
authors: Teresa M
authors: TM
authors: De Caralt
authors: Rosario J
authors: RJ
authors: Perea
authors: Julio
authors: J
authors: Pascual
authors: María José
authors: MJ
authors: Soler
mesh_terms: D000368:Aged; D000085962:Angiotensin-Converting Enzyme 2; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000097:blood / Q000201:enzymology / Q000503:physiopathology*; D009206:Myocardium / Q000473:pathology; D007703:Peptidyl-Dipeptidase A / Q000097:blood*; D011446:Prospective Studies; D012307:Risk Factors; D013318:Stroke Volume; D020257:Ventricular Remodeling
chemical_list: D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2
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