title: New perspectives in the renin-angiotensin-aldosterone system (RAAS) II: albumin suppresses angiotensin converting enzyme (ACE) activity in human.
abstract: About 8% of the adult population is taking angiotensin-converting enzyme (ACE) inhibitors to treat cardiovascular disease including hypertension, myocardial infarction and heart failure. These drugs decrease mortality by up to one-fifth in these patients. We and others have reported previously that endogenous inhibitory substances suppress serum ACE activity, in vivo, similarly to the ACE inhibitor drugs. Here we have made an effort to identify this endogenous ACE inhibitor substance. ACE was crosslinked with interacting proteins in human sera. The crosslinked products were immunoprecipitated and subjected to Western blot. One of the crosslinked products was recognized by both anti-ACE and anti-HSA (human serum albumin) antibodies. Direct ACE-HSA interaction was confirmed by binding assays using purified ACE and HSA. HSA inhibited human purified (circulating) and human recombinant ACE with potencies (IC50) of 5.7 ± 0.7 and 9.5 ± 1.1 mg/mL, respectively. Effects of HSA on the tissue bound native ACE were tested on human saphenous vein samples. Angiotensin I evoked vasoconstriction was inhibited by HSA in this vascular tissue (maximal force with HSA: 6.14 ± 1.34 mN, without HSA: 13.54 ± 2.63 mN), while HSA was without effects on angiotensin II mediated constrictions (maximal force with HSA: 18.73 ± 2.17 mN, without HSA: 19.22 ± 3.50 mN). The main finding of this study is that HSA was identified as a potent physiological inhibitor of the ACE. The enzymatic activity of ACE appears to be almost completely suppressed by HSA when it is present in its physiological concentration. These data suggest that angiotensin I conversion is limited by low physiological ACE activities, in vivo.
authors.affiliation: Division of Clinical Physiology, Institute of Cardiology, University of Debrecen, Debrecen, Hungary.
authors.forename: Miklós
authors.initials: M
authors.lastname: Fagyas
authors.affiliation: Division of Clinical Physiology, Institute of Cardiology, University of Debrecen, Debrecen, Hungary.
authors.forename: Katalin
authors.initials: K
authors.lastname: Úri
authors.affiliation: Division of Clinical Physiology, Institute of Cardiology, University of Debrecen, Debrecen, Hungary.
authors.forename: Ivetta M
authors.initials: IM
authors.lastname: Siket
authors.affiliation: Division of Clinical Physiology, Institute of Cardiology, University of Debrecen, Debrecen, Hungary.
authors.forename: Gábor Á
authors.initials: GÁ
authors.lastname: Fülöp
authors.affiliation: Division of Clinical Physiology, Institute of Cardiology, University of Debrecen, Debrecen, Hungary.
authors.forename: Viktória
authors.initials: V
authors.lastname: Csató
authors.affiliation: Division of Clinical Physiology, Institute of Cardiology, University of Debrecen, Debrecen, Hungary.
authors.forename: Andrea
authors.initials: A
authors.lastname: Daragó
authors.affiliation: Department of Neurology, University of Debrecen, Debrecen, Hungary.
authors.forename: Judit
authors.initials: J
authors.lastname: Boczán
authors.affiliation: Institute of Internal Medicine, Division of Nephrology, University of Debrecen, Debrecen, Hungary.
authors.forename: Emese
authors.initials: E
authors.lastname: Bányai
authors.affiliation: Department of Cardiac Surgery, Institute of Cardiology, University of Debrecen, Debrecen, Hungary.
authors.forename: István Elek
authors.initials: IE
authors.lastname: Szentkirályi
authors.affiliation: Department of Cardiac Surgery, Institute of Cardiology, University of Debrecen, Debrecen, Hungary.
authors.forename: Tamás Miklós
authors.initials: TM
authors.lastname: Maros
authors.affiliation: Department of Cardiac Surgery, Institute of Cardiology, University of Debrecen, Debrecen, Hungary.
authors.forename: Tamás
authors.initials: T
authors.lastname: Szerafin
authors.affiliation: Division of Clinical Physiology, Institute of Cardiology, University of Debrecen, Debrecen, Hungary.
authors.forename: István
authors.initials: I
authors.lastname: Édes
authors.affiliation: Division of Clinical Physiology, Institute of Cardiology, University of Debrecen, Debrecen, Hungary.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Papp
authors.affiliation: Division of Clinical Physiology, Institute of Cardiology, University of Debrecen, Debrecen, Hungary.
authors.forename: Attila
authors.initials: A
authors.lastname: Tóth
mesh_terms: D000803:Angiotensin I / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D001696:Biomechanical Phenomena / Q000187:drug effects; D020134:Catalytic Domain; D006801:Humans; D007700:Kinetics; D008970:Molecular Weight; D007703:Peptidyl-Dipeptidase A / Q000097:blood*; D011994:Recombinant Proteins / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects*; D012501:Saphenous Vein / Q000187:drug effects / Q000201:enzymology; D012709:Serum Albumin / Q000494:pharmacology*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D011994:Recombinant Proteins; D012709:Serum Albumin; D000803:Angiotensin I; C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A