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dc.contributor.authorDanilov, Sergei M
dc.contributor.authorLünsdorf, Heinrich
dc.contributor.authorAkinbi, Henry T
dc.contributor.authorNesterovitch, Andrew B
dc.contributor.authorEpshtein, Yuliya
dc.contributor.authorLetsiou, Eleftheria
dc.contributor.authorKryukova, Olga V
dc.contributor.authorPiegeler, Tobias
dc.contributor.authorGolukhova, Elena Z
dc.contributor.authorSchwartz, David E
dc.contributor.authorDull, Randal O
dc.contributor.authorMinshall, Richard D
dc.contributor.authorKost, Olga A
dc.contributor.authorGarcia, Joe G N
dc.date.accessioned2016-11-18T10:20:16Z
dc.date.available2016-11-18T10:20:16Z
dc.date.issued2016-10-13
dc.identifier.citationLysozyme and bilirubin bind to ACE and regulate its conformation and shedding. 2016, 6:34913 Sci Repen
dc.identifier.issn2045-2322
dc.identifier.pmid27734897
dc.identifier.doi10.1038/srep34913
dc.identifier.urihttp://hdl.handle.net/10033/620587
dc.description.abstractAngiotensin I-converting enzyme (ACE) hydrolyzes numerous peptides and is a critical participant in blood pressure regulation and vascular remodeling. Elevated tissue ACE levels are associated with increased risk for cardiovascular and respiratory disorders. Blood ACE concentrations are determined by proteolytic cleavage of ACE from the endothelial cell surface, a process that remains incompletely understood. In this study, we identified a novel ACE gene mutation (Arg532Trp substitution in the N domain of somatic ACE) that increases blood ACE activity 7-fold and interrogated the mechanism by which this mutation significantly increases blood ACE levels. We hypothesized that this ACE mutation disrupts the binding site for blood components which may stabilize ACE conformation and diminish ACE shedding. We identified the ACE-binding protein in the blood as lysozyme and also a Low Molecular Weight (LMW) ACE effector, bilirubin, which act in concert to regulate ACE conformation and thereby influence ACE shedding. These results provide mechanistic insight into the elevated blood level of ACE observed in patients on ACE inhibitor therapy and elevated blood lysozyme and ACE levels in sarcoidosis patients.
dc.languageENG
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleLysozyme and bilirubin bind to ACE and regulate its conformation and shedding.
dc.typeArticleen
dc.contributor.departmentHelmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.en
dc.identifier.journalScientific reportsen
refterms.dateFOA2018-06-12T23:49:12Z
html.description.abstractAngiotensin I-converting enzyme (ACE) hydrolyzes numerous peptides and is a critical participant in blood pressure regulation and vascular remodeling. Elevated tissue ACE levels are associated with increased risk for cardiovascular and respiratory disorders. Blood ACE concentrations are determined by proteolytic cleavage of ACE from the endothelial cell surface, a process that remains incompletely understood. In this study, we identified a novel ACE gene mutation (Arg532Trp substitution in the N domain of somatic ACE) that increases blood ACE activity 7-fold and interrogated the mechanism by which this mutation significantly increases blood ACE levels. We hypothesized that this ACE mutation disrupts the binding site for blood components which may stabilize ACE conformation and diminish ACE shedding. We identified the ACE-binding protein in the blood as lysozyme and also a Low Molecular Weight (LMW) ACE effector, bilirubin, which act in concert to regulate ACE conformation and thereby influence ACE shedding. These results provide mechanistic insight into the elevated blood level of ACE observed in patients on ACE inhibitor therapy and elevated blood lysozyme and ACE levels in sarcoidosis patients.


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