title: Circulating ACE2 activity is increased in patients with type 1 diabetes and vascular complications.
abstract: OBJECTIVE
  Angiotensin-converting enzyme 2 (ACE2) is a homolog of ACE that counterbalances the actions of angiotensin (AT)II and promotes vasodilatation. Circulating ACE2 activity is increased in diabetes in experimental models. The role of ACE2 in human pathophysiology is unknown. We examined whether ACE2 activity is altered in patients with type 1 diabetes (T1D), with and without diabetic nephropathy.
  
  
  METHODS
  Quantitative ACE2 activity in serum was measured by a fluorometric assay in 859 patients with T1D in the Finnish Diabetic Nephropathy (FinnDiane) study and in 204 healthy controls. Pulse-wave analysis with augmentation index (AIx) measurement was performed in 319 patients with T1D and 114 controls.
  
  
  RESULTS
  ACE2 activity was increased in men with T1D and microalbuminuria (30.2 ± 1.5 ngE/ml) when compared to patients without albuminuria (27.0 ± 0.5 ngE/ml, P < 0.05) or controls (25.6 ± 0.8 ngE/ml, P < 0.05). ACE2 activity was increased in male and female patients who were on ACE inhibitor (ACEi) treatment, also independently of albuminuria. Male and female patients with coronary heart disease (CHD) had significantly increased ACE2 activity (35.5 ± 2.5 vs. 27.0 ± 0.5 ngE/ml, P < 0.001 among male T1D patients vs. male controls). ACE2 activity correlated positively with systolic blood pressure (rs = 0.175, P < 0.001), AIx (rs = 0.191, P = 0.010) and diabetes duration (rs = 0.198, P < 0.001), and negatively with estimated glomerular filtration rate (rs = -0.109, P = 0.016) among male T1D patients.
  
  
  CONCLUSIONS
  ACE2 activity increases with increasing vascular tone and when the patient with T1D has microvascular or macrovascular disease, indicating that ACE2 may participate as a compensatory mechanism in the regulation of vascular and renal function in patients with T1D.
authors.affiliation: Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, and Folkhälsan Research Center, Helsinki, Finland.
authors.forename: Aino
authors.initials: A
authors.lastname: Soro-Paavonen
authors.forename: Daniel
authors.initials: D
authors.lastname: Gordin
authors.forename: Carol
authors.initials: C
authors.lastname: Forsblom
authors.forename: Milla
authors.initials: M
authors.lastname: Rosengard-Barlund
authors.forename: Johan
authors.initials: J
authors.lastname: Waden
authors.forename: Lena
authors.initials: L
authors.lastname: Thorn
authors.forename: Niina
authors.initials: N
authors.lastname: Sandholm
authors.forename: Merlin C
authors.initials: MC
authors.lastname: Thomas
authors.forename: Per-Henrik
authors.initials: PH
authors.lastname: Groop
mesh_terms: D000328:Adult; D000085962:Angiotensin-Converting Enzyme 2; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000150:complications / Q000201:enzymology*; D003925:Diabetic Angiopathies / Q000097:blood / Q000201:enzymology*; D005260:Female; D006801:Humans; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000097:blood*
chemical_list: D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2