Inhibition of human peptidyl dipeptidase (angiotensin I converting enzyme: kininase II) by human serum albumin and its fragments.

Klauser, R.; Robinson, Courtland; Marinkovic, Dobrivoje V.; Erdös, Ervin G.

doi:10.1161/01.hyp.1.3.281

Cited by 30 publications

(18 citation statements)

References 22 publications

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“…Existence of endogenous ACE (called kininase II at this time) inhibitors were proposed as early as 1979. Klauser et al reported that plasma preparations and human serum albumin inhibit the ACE [20], which was also confirmed by us [40] while Ryan et al reported that small (<10 kDa) molecular weight components of human sera and urine are also able to inhibit purified ACE [21]. These original reports were followed by some reports suggesting that substrate analogues (such as angiotensin I [22] and substance P [23]) can also inhibit ACE.…”

Section: Discussionmentioning

confidence: 72%

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New Perspectives in the Renin-Angiotensin-Aldosterone System (RAAS) I: Endogenous Angiotensin Converting Enzyme (ACE) Inhibition

et al. 2014

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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±0.7 U/L at 4-fold dilution, 51.4±0.3 U/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±145 U/L, 605±42 U/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±2.4 U/L, n = 4, control: 26.4±0.7 U/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.

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Section: Discussionmentioning

confidence: 72%

“…It has been reported that human serum albumin [20] and small (<10 kDa) molecules [21] can inhibit ACE. Several more inhibitors has been suggested afterward.…”

Section: Introductionmentioning

confidence: 99%

New Perspectives in the Renin-Angiotensin-Aldosterone System (RAAS) I: Endogenous Angiotensin Converting Enzyme (ACE) Inhibition

et al. 2014

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“…It is believed that the serum ACE level reflects the total granulomatous load. This level may be influenced by the presence of specific or nonspecific ACE inhibitors such as albumin and its fragments, fibrinolytic products, insulin including its beta chain (Klauser et al 1979). Immunoassays of ACE concentration avoid this problem and allow the calculation of the specific activity of ACE.…”

Section: Wwwintechopencommentioning

confidence: 99%

Diagnosis of Pulmonary Sarcoidosis

Shulimzon¹,

Koslow²

2011

Sarcoidosis Diagnosis and Management

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“…This observation led to the synthesis of angiotensin-converting enzyme inhibitors (ACEI). Bradykinin-potentiating and ACE-inhibiting peptides have also been found in a number of other crotaline venoms [10] [11]. So far, least work has been done in India on complications and cardiotoxicity profile following poisonous snake bite.…”

Section: Introductionmentioning

confidence: 99%

A Study of Cardiac Profile in Patients with Snake Envenomation and Its Complications

Ramakrishna¹,

Kanattu²

2017

IJCM

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Background: Snake bite is a common and frequently devastating environmental and occupational disease, especially in rural areas of tropical developing countries. The present study was undertaken to evaluate the effect on cardiac profile in patients with snake envenomation and its complications. Methods: A total of 200 patients with snake envenomation were enrolled in this study excluding patients having history of any cardiovascular disease, renal disease, coagulopathy, liver disease, neuromuscular disease and those cases who bitten by non-poisonous snakes. All patients underwent physical examination, laboratory, Electrocardiogram (ECG), X-ray of chest and echocardiogram investigations. Results: A total of 200 cases had envenomation having 116 (58%) of male subjects. Most common local signs were edema 187 (93.5%), tenderness 141 (70.5%), skin necrosis 81 (40.5%) and blistering 12 (6%). Severity of local envenomation was graded into mild 66 (33%), moderate 120 (60%) and severe 14 (7%) cases. Systemic manifestations were present in 83 patients of venomous bites. It includes that majorly 53 (26.5%) cases had vomiting, 44 (22%) cases had abdominal pain and 9 (4.5%) cases of hypotension. ECG manifestation showed 27 (13.5%), 6 (3%) and 1 (0.5%) patients had sinus tachycardia, sinus bradycardia and ventricular tachycardia respectively. While, 9 (4.5%) cases had T inversion alone in precordial leads. Mortality (3%) was observed in intracranial bleed, neurotoxicity and capillary leak syndrome. However, cardiovascular involvement was not responsible for mortality in any cases. Conclusion: In conclusion, ventricular tachycardia is one of the manifestations of snake envenomation. Moreover, sinus tachycardia is common cardiovascular sign which may not be due to cardiac causes. Mortality results conclude that, cardiovascular involvement could not be responsible for mortality in snake envenomation.

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Inhibition of human peptidyl dipeptidase (angiotensin I converting enzyme: kininase II) by human serum albumin and its fragments.

Cited by 30 publications

References 22 publications

New Perspectives in the Renin-Angiotensin-Aldosterone System (RAAS) I: Endogenous Angiotensin Converting Enzyme (ACE) Inhibition

New Perspectives in the Renin-Angiotensin-Aldosterone System (RAAS) I: Endogenous Angiotensin Converting Enzyme (ACE) Inhibition

Diagnosis of Pulmonary Sarcoidosis

A Study of Cardiac Profile in Patients with Snake Envenomation and Its Complications

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