ArticleBiomolecules2019
Novel Variants of Angiotensin Converting Enzyme-2 of Shorter Molecular Size to Target the Kidney Renin Angiotensin System.
Article in Biomolecules, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- Pooled it
- Proximal tubule ACE2 mediates early responses to hypertension by regulating intrarenal RAS and sodium homeostasis.JCI insight · 2026Article
- Protective Arm of Renin-Angiotensin System: Evidence of Nephroprotective Effects Against Acute Kidney Injury.Acta physiologica (Oxford, England) · 2026Review
- Fecal ACE and ACE2 Activities Reflect Intestinal Shedding and Microbiota Modulation of Renin-Angiotensin System.Biology · 2026Article
- Aminopeptidase A Effect on Angiotensin Peptides and Their Blood Pressure Action.International journal of molecular sciences · 2025Article
- ACE2, From the Kidney to SARS-CoV-2: Donald Seldin Award Lecture 2023.Hypertension (Dallas, Tex. : 1979) · 2025Article
- ACE2 and TMPRSS2 in human kidney tissue and urine extracellular vesicles with age, sex, and COVID-19.Pflugers Archiv : European journal of physiology · 2025Article
- Altered kidney distribution and loss of ACE2 into the urine in acute kidney injury.American journal of physiology. Renal physiology · 2024Article
- Urinary angiotensin-converting enzyme 2 and its activity in cats with chronic kidney disease.Frontiers in veterinary science · 2024Article
- Canine Coronavirus Infection Modulates the Biogenesis and Composition of Cell-Derived Extracellular Vesicles.Biomedicines · 2023Article
- ACE2 in the Urine: Where Does It Come From?Kidney360 · 2022Article
- Article
- A Novel Soluble ACE2 Protein Provides Lung and Kidney Protection in Mice Susceptible to Lethal SARS-CoV-2 Infection.Journal of the American Society of Nephrology : JASN · 2022Article
- Kidney Angiotensin in Cardiovascular Disease: Formation and Drug Targeting.Pharmacological reviews · 2022Review
- The innate immune response, microenvironment proteinases, and the COVID-19 pandemic: pathophysiologic mechanisms and emerging therapeutic targets.Kidney international supplements · 2022Review
- An Adverse Outcomes Approach to Study the Effects of SARS-CoV-2 in 3D Organoid Models.Journal of molecular biology · 2022Review
- Epicatechin is a promising novel inhibitor of SARS-CoV-2 entry by disrupting interactions between angiotensin-converting enzyme type 2 and the viral receptor binding domain: A computational/simulation study.Computers in biology and medicine · 2022Article
- An ACE2-IgG4 Fc Fusion Protein Demonstrates Strong Binding to All Tested SARS-CoV-2 Variants and Reduced Lung Inflammation in Animal Models of SARS-CoV-2 and Influenza.Pathogens & immunity · 2022Article
- Angiotensin-Converting Enzyme 2 (ACE2) in the Context of Respiratory Diseases and Its Importance in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Potent prophylactic and therapeutic efficacy of recombinant human ACE2-Fc against SARS-CoV-2 infection in vivo.Cell discovery · 2021Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 2 countries.
Funding
Abstract
ACE2 is a monocarboxypeptidase which generates Angiotensin (1-7) from Angiotensin II (1-8). Attempts to target the kidney Renin Angiotensin System using native ACE2 to treat kidney disease are hampered by its large molecular size, 100 kDa, which precludes its glomerular filtration and subsequent tubular uptake. Here, we show that both urine and kidney lysates are capable of digesting native ACE2 into shorter proteins of ~60-75 kDa and then demonstrate that they are enzymatically very active. We then truncated the native ACE2 by design from the C-terminus to generate two short recombinant (r)ACE2 variants (1-605 and 1-619AA). These two truncates have a molecular size of ~70 kDa, as expected from the amino acid sequence and as shown by Western blot. ACE2 enzyme activity, measured using a specific substrate, was higher than that of the native rACE2 (1-740 AA). When infused to mice with genetic ACE2 deficiency, a single i.v. injection of 1-619 resulted in detectable ACE2 activity in urine, whereas infusion of the native ACE2 did not. Moreover, ACE2 activity was recovered in harvested kidneys from ACE2-deficient mice infused with 1-619, but not in controls (23.1 ± 4.3 RFU/µg creatinine/h and 1.96 ± 0.73 RFU/µg protein/hr, respectively). In addition, the kidneys of ACE2-null mice infused with 1-619 studied ex vivo formed more Ang (1-7) from exogenous Ang II than those infused with vehicle (AUC 8555 ± 1933 vs. 3439 ± 753 ng/mL, respectively,
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Registered trials
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.