New perspectives in the renin-angiotensin-aldosterone system (RAAS) III: Endogenous inhibition of angiotensin converting enzyme (ACE) provides protection against cardiovascular diseases

Miklos Fagyas, Katalin Úri, Ivetta M. Siket, Andrea Daragó, Judit Boczán, Emese Bányai, I. Édes, Z. Papp, Attila Tóth

Research output: Contribution to journalArticle

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Abstract

ACE inhibitor drugs decrease mortality by up to one-fifth in cardiovascular patients. Surprisingly, there are reports dating back to 1979 suggesting the existence of endogenous ACE inhibitors. Here we investigated the clinical significance of this potential endogenous ACE inhibition. ACE concentration and activity was measured in patient's serum samples (n = 151). ACE concentration was found to be in a wide range (47-288 ng/mL). ACE activity decreased with the increasing concentration of the serum albumin (HSA): ACE activity was 56±1 U/L in the presence of 2.4±0.3 mg/mL HSA, compared to 39±1 U/L in the presence of 1261 mg/mL HSA (values are mean±SEM). Effects of the differences in ACE concentration were suppressed in human sera: patients with ACE DD genotype exhibited a 64% higher serum ACE concentration (range, 74-288 ng/mL, median, 155.2 ng/mL, n = 52) compared to patients with II genotype (range, 47-194 ng/mL, median, 94.5 ng/mL, n = 28) while the difference in ACE activities was only 32% (range, 27.3-59.8 U/L, median, 43.11 U/L, and range 15.6-55.4 U/L, median, 32.74 U/L, respectively) in the presence of 12±1 mg/mL HSA. No correlations were found between serum ACE concentration (or genotype) and cardiovascular diseases, in accordance with the proposed suppressed physiological ACE activities by HSA (concentration in the sera of these patients: 48.5±0.5 mg/mL) or other endogenous inhibitors. Main implications are that (1) physiological ACE activity can be stabilized at a low level by endogenous ACE inhibitors, such as HSA; (2) angiotensin II elimination may have a significant role in angiotensin II related pathologies.

Original languageEnglish
Article numbere93719
JournalPLoS One
Volume9
Issue number4
DOIs
Publication statusPublished - Apr 1 2014

Fingerprint

angiotensins
renin
aldosterone
peptidyl-dipeptidase A
Angiotensins
Peptidyl-Dipeptidase A
Renin-Angiotensin System
Aldosterone
Renin
cardiovascular diseases
Cardiovascular Diseases
Enzyme activity
enzyme activity
Angiotensin-Converting Enzyme Inhibitors
Serum
angiotensin II
Genotype
Angiotensin II
genotype
Enzyme inhibition

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

New perspectives in the renin-angiotensin-aldosterone system (RAAS) III : Endogenous inhibition of angiotensin converting enzyme (ACE) provides protection against cardiovascular diseases. / Fagyas, Miklos; Úri, Katalin; Siket, Ivetta M.; Daragó, Andrea; Boczán, Judit; Bányai, Emese; Édes, I.; Papp, Z.; Tóth, Attila.

In: PLoS One, Vol. 9, No. 4, e93719, 01.04.2014.

Research output: Contribution to journalArticle

Fagyas, Miklos ; Úri, Katalin ; Siket, Ivetta M. ; Daragó, Andrea ; Boczán, Judit ; Bányai, Emese ; Édes, I. ; Papp, Z. ; Tóth, Attila. / New perspectives in the renin-angiotensin-aldosterone system (RAAS) III : Endogenous inhibition of angiotensin converting enzyme (ACE) provides protection against cardiovascular diseases. In: PLoS One. 2014 ; Vol. 9, No. 4.
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