title: Circulating ACE2 activity correlates with cardiovascular disease development.
abstract: It was shown recently that angiotensin-converting enzyme activity is limited by endogenous inhibition in vivo, highlighting the importance of angiotensin II (ACE2) elimination. The potential contribution of the ACE2 to cardiovascular disease progression was addressed. Serum ACE2 activities were measured in different clinical states (healthy, n=45; hypertensive, n=239; heart failure (HF) with reduced ejection fraction (HFrEF) n=141 and HF with preserved ejection fraction (HFpEF) n=47). ACE2 activity was significantly higher in hypertensive patients (24.8±0.8 U/ml) than that in healthy volunteers (16.2±0.8 U/ml, p=0.01). ACE2 activity further increased in HFrEF patients (43.9±2.1 U/ml, p=0.001) but not in HFpEF patients (24.6±1.9 U/ml) when compared with hypertensive patients. Serum ACE2 activity negatively correlated with left ventricular systolic function in HFrEF, but not in hypertensive, HFpEF or healthy populations. Serum ACE2 activity had a fair diagnostic value to differentiate HFpEF from HFrEF patients in this study. Serum ACE2 activity correlates with cardiovascular disease development: it increases when hypertension develops and further increases when the cardiovascular disease further progresses to systolic dysfunction, suggesting that ACE2 metabolism plays a role in these processes. In contrast, serum ACE2 activity does not change when hypertension progresses to HFpEF, suggesting a different pathomechanism for HFpEF, and proposing a biomarker-based identification of these HF forms.
authors.affiliation: Department of Clinical Physiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: Katalin
authors.initials: K
authors.lastname: Úri
authors.affiliation: Department of Clinical Physiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.|Department of Cardiology, Institute of Cardiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: Miklós
authors.initials: M
authors.lastname: Fagyas
authors.affiliation: Department of Cardiology, Institute of Cardiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: Attila
authors.initials: A
authors.lastname: Kertész
authors.affiliation: Department of Cardiology, Institute of Cardiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: Attila
authors.initials: A
authors.lastname: Borbély
authors.affiliation: Department of Cardiology, Institute of Cardiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: Csaba
authors.initials: C
authors.lastname: Jenei
authors.affiliation: Department of Cardiology, Institute of Cardiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: Orsolya
authors.initials: O
authors.lastname: Bene
authors.affiliation: Department of Cardiology, Institute of Cardiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Csanádi
authors.affiliation: Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Paulus
authors.affiliation: Department of Cardiology, Institute of Cardiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: István
authors.initials: I
authors.lastname: Édes
authors.affiliation: Department of Clinical Physiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Papp
authors.affiliation: Department of Clinical Physiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: Attila
authors.initials: A
authors.lastname: Tóth
authors.affiliation: Department of Clinical Physiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary lizanecz@yahoo.com.|Department of Cardiology, Institute of Cardiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: Erzsébet
authors.initials: E
authors.lastname: Lizanecz
mesh_terms: D000328:Adult; D000368:Aged; D000085962:Angiotensin-Converting Enzyme 2; D002318:Cardiovascular Diseases / Q000097:blood* / Q000201:enzymology* / Q000503:physiopathology; D015331:Cohort Studies; D015897:Comorbidity; D003971:Diastole; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000503:physiopathology; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D007703:Peptidyl-Dipeptidase A / Q000097:blood*; D011379:Prognosis; D012372:ROC Curve; D013599:Systole
chemical_list: D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2
keywords: Angiotensin-converting enzyme 2; biomarker; diastolic heart failure; hypertension; renin–angiotensin–aldosterone system; systolic heart failure