Trial reportThe Journal of clinical investigation1996
Acute angiotensin-converting enzyme inhibition increases the plasma level of the natural stem cell regulator N-acetyl-seryl-aspartyl-lysyl-proline.
Trial report in The Journal of clinical investigation, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
85 citing papers in PubMed, 3 syntheses or guidelines pooled it, 339 citations in OpenAlex.
- UK kidney association clinical practice guideline: update of anaemia of chronic kidney disease.BMC nephrology · 2025Guideline
- A systematic review and meta-analysis of factors contributing to post-kidney transplant anemia and the effect of erythropoietin-stimulating agents.Systematic reviews · 2024Pooled it
- Pooled it
- Ac-SDKP and eplerenone confer additive cardioprotection against angiotensin II-induced cardiac injury in C57BL/6J mice.Journal of molecular and cellular cardiology plus · 2025Article
- Verification of haemoglobin level to prevent worsening of prognosis in heart failure with preserved ejection fraction patients from the PURSUIT-HFpEF registry.ESC heart failure · 2024Observational
- Hematological parameters of hypertensive patients in northeast Ethiopia: A comparative cross-sectional study.Heliyon · 2024Article
- Ac-SDKP attenuates ER stress-stimulated collagen production in cardiac fibroblasts by inhibiting CHOP-mediated NF-κB expression.Frontiers in pharmacology · 2024Article
- Knockout of ACE-N facilitates improved cardiac function after myocardial infarction.Journal of molecular and cellular cardiology plus · 2023Article
- Pocket ACEs: Discovering new function within an old player.Frontiers in physiology · 2023Review
- Structural basis for the inhibition of human angiotensin-1 converting enzyme by fosinoprilat.The FEBS journal · 2022Article
- The Role of Tβ4-POP-Ac-SDKP Axis in Organ Fibrosis.International journal of molecular sciences · 2022Review
- Erythropoietin-Stimulating Agent Hyporesponsiveness in Patients Living with Chronic Kidney Disease.Kidney diseases (Basel, Switzerland) · 2022Review
- Efficacy and safety of recombinant human erythropoietin (Hema-PlusWorld journal of nephrology · 2021Article
- Angiotensin-converting enzyme open for business: structural insights into the subdomain dynamics.The FEBS journal · 2021Article
- Role of Kinins in Hypertension and Heart Failure.Pharmaceuticals (Basel, Switzerland) · 2020Review
- Protective role of ACE2 and its downregulation in SARS-CoV-2 infection leading to Macrophage Activation Syndrome: Therapeutic implications.Life sciences · 2020Review
- Anemia and iron deficiency among chronic kidney disease Stages 3-5ND patients in the Chronic Kidney Disease Outcomes and Practice Patterns Study: often unmeasured, variably treated.Clinical kidney journal · 2020Article
- N-acetyl-seryl-aspartyl-lysyl-proline is a valuable endogenous antifibrotic peptide for kidney fibrosis in diabetes: An update and translational aspects.Journal of diabetes investigation · 2020Review
- Role of angiotensin-converting enzyme in myeloid cell immune responses.Cellular & molecular biology letters · 2020Review
- N-Acetyl-Seryl-Aspartyl-Lysyl-Proline Mitigates Experimental Colitis Through Inhibition of Intestinal Mucosal Inflammatory ResponsesFrontiers in pharmacology · 2020Article
25 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Angiotensin I-converting enzyme (ACE) has two homologous active NH2- and COOH-terminal domains and displays activity toward a broad range of substrates. The tetrapeptide N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) has been shown to be hydrolyzed in vitro by ACE and to be a preferential substrate for its NH2-terminal active site. This peptide is a regulatory factor of hematopoiesis which reversibly stem cells and normal early progenitors into S-phase. We found that a single oral dose of 50 mg of the ACE inhibitor, captopril, when administered to eight healthy subjects in a double-blind, crossover, placebo-controlled study, massively increased the plasma level of Ac-SDKP. ACE inhibition by captopril induced a 90-99% inhibition of in vitro [3H]Ac-SDKP hydrolysis and a long-lasting 5.5-fold (range: 4-8.5-fold) increase in the plasma levels of Ac-SDKP. These results demonstrate that Ac-SDKP is the first natural peptide hydrolyzed by the NH2-terminal domain of ACE not only in vitro but also in vivo, confirming that both catalytic sites of ACE are physiologically active. Our data suggest that ACE may also be implicated in the process of hematopoietic stem cell regulation, by permanently degrading this natural circulating inhibitor of cell entry into S-phase.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.