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001-es BibID:	BIBFORM050118
035-os BibID:	Article ID: e87843
Első szerző:	Fagyas Miklós (orvos)
Cím:	New perspectives in the renin-angiotensin-aldosterone system (RAAS) I : endogenous angiotensin converting enzyme (ACE) inhibition / Miklós Fagyas, Katalin Úri, Ivetta M. Siket, Andrea Daragó, Judit Boczán, Emese Bányai, István Édes, Zoltán Papp, Attila Tóth
Dátum:	2014
ISSN:	1932-6203
Megjegyzések:	Angiotensin-converting enzyme (ACE) inhibitors represent the fifth most often prescribed drugs. ACE inhibitors decrease 5-year mortality by approximately one-fifth in cardiovascular patients. Surprisingly, there are reports dating back to 1979 suggesting the existence of endogenous ACE inhibitors, which endogenous inhibitory effects are much less characterized than that for the clinically administered ACE inhibitors. Here we aimed to investigate this endogenous ACE inhibition in human sera. It was hypothesized that ACE activity is masked by an endogenous inhibitor, which dissociates from the ACE when its concentration decreases upon dilution. ACE activity was measured by FAPGG hydrolysis first. The specific (dilution corrected) enzyme activities significantly increased by dilution of human serum samples (23.2?0.7U/L at 4-fold dilution, 51.4?0.3U/L at 32-fold dilution, n=3, p=0.001), suggesting the presence of an endogenous inhibitor. In accordance, specific enzyme activities did not changed by dilution when purified renal ACE was used, where no endogenous inhibitor was present (655?145U/L, 605?42U/L, n=3, p=0.715, respectively). FAPGG conversion strongly correlated with angiotensin I conversion suggesting that this feature is not related to the artificial substrate. Serum samples were ultra-filtered to separate ACE (MW: 180 kDa) and the hypothesized inhibitor. Filtering through 50 kDa filters was without effect, while filtering through 100 kDa filters eliminated the inhibiting factor (ACE activity after <100 kDa filtering: 56.4?2.4U/L, n=4, control: 26.4?0.7U/L, n=4, p<0.001). Lineweaver-Burk plot indicated non-competitive inhibition of ACE by this endogenous factor. The endogenous inhibitor had higher potency on the C-terminal active site than N-terminal active site of ACE. Finally, this endogenous ACE inhibition was also present in mouse, donkey, goat, bovine sera besides men (increasing of specific ACE activity from 4-fold to 32-fold dilution: 2.8-fold, 1.7-fold, 1.5-fold, 1.8-fold, 2.6-fold, respectively). We report here the existence of an evolutionary conserved mechanism suppressing circulating ACE activity, in vivo, similarly to ACE inhibitory drugs.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban ACE angiotensin-converting enzyme renin-angiotensin-aldosterone system endogenous ACE inhibition Molekuláris Medicina
Megjelenés:	Plos One. - 9 : 4 (2014), p. 1-29. -
További szerzők:	Úri Katalin Mányiné Siket Ivetta (1962-) (laborasszisztens) Daragó Andrea (1972-) (orvos, kardiológus) Boczán Judit (1972-) (neurológus) Bányai Emese (1984-) (orvos) Édes István (1952-) (kardiológus) Papp Zoltán (1965-) (kardiológus, élettanász) Tóth Attila (1971-) (biológus)
Pályázati támogatás:	TÁMOP-4.2.1/B-09/1/KONV-2010-0007 TÁMOP Vaszkuláris tranziens receptor potenciál (TRP) csatornák TÁMOP-4.2.2.A-11/1/KONV-2012-0045 TÁMOP Kardiológia Kutatócsoport K84300 OTKA
Internet cím:	DOI Intézményi repozitóriumban (DEA) tárolt változat
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