New Perspectives in the Renin-Angiotensin-Aldosterone System RAAS II: Albumin Suppresses Angiotensin Converting Enzyme ACE Activity in HumanReport as inadecuate




New Perspectives in the Renin-Angiotensin-Aldosterone System RAAS II: Albumin Suppresses Angiotensin Converting Enzyme ACE Activity in Human - Download this document for free, or read online. Document in PDF available to download.

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.



Author: Miklós Fagyas, Katalin Úri, Ivetta M. Siket, Gábor Á. Fülöp, Viktória Csató, Andrea Daragó, Judit Boczán, Emese Bányai

Source: http://plos.srce.hr/



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