title: High plasma level of N-acetyl-seryl-aspartyl-lysyl-proline: a new marker of chronic angiotensin-converting enzyme inhibition.
abstract: The acute administration of the angiotensin-converting enzyme (ACE) inhibitor captopril to healthy subjects transiently increases 5.5-fold the plasma levels of a natural stem-cell regulator, N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP). The aim of this study was to measure plasma Ac-SDKP levels during chronic treatment with all types of ACE inhibitors and to assess its relevance as a marker of ACE inhibition. Plasma levels of Ac-SDKP were blindly determined in age- and sex-matched hypertensive patients either treated (ACEI group, n=27) or not (non-ACEI group, n=23) with an ACE inhibitor for more than 1 month. Geometric mean [range] of plasma Ac-SDKP levels were significantly higher in the ACEI group (3.78 [1.48 to 14.5] pmol/mL) than in the non-ACEI group, with no overlap between the groups (0.75 [0.36 to 1.22] pmol/mL, P<.0001). The measurement of Ac-SDKP in plasma discriminated all the patients of the ACEI group, whereas the simultaneous determination of either in vitro (using hippuryl-histidine-leucine as substrate) or in vivo (angiotensin II/angiotensin I ratio) ACE activity failed to identify nine and five cases, respectively. We conclude that Ac-SDKP accumulates in plasma during chronic ACE inhibitor treatment. The long-term consequences of Ac-SDKP accumulation are unknown. The reliability of plasma Ac-SDKP measurement makes it the best marker of chronic ACE inhibition, which can help to verify patients' compliance to ACE inhibitor treatment.
authors.affiliation: Broussais Hospital Clinical Investigation Center, INSERM, and Assistance Publique des Hôpitaux de Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Azizi
authors.forename: E
authors.initials: E
authors.lastname: Ezan
authors.forename: L
authors.initials: L
authors.lastname: Nicolet
authors.forename: J M
authors.initials: JM
authors.lastname: Grognet
authors.forename: J
authors.initials: J
authors.lastname: Ménard
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000450:Aldosterone / Q000097:blood; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000809:Angiotensins / Q000097:blood; D015415:Biomarkers / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000097:blood*; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000502:physiology; D012680:Sensitivity and Specificity; D013997:Time Factors
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000809:Angiotensins; D015415:Biomarkers; D009842:Oligopeptides; D000450:Aldosterone; D007703:Peptidyl-Dipeptidase A; D012083:Renin; C058504:goralatide