ArticleCirculation research2017
Clinical Relevance and Role of Neuronal AT
Article in Circulation research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 122 papers, 3 of them syntheses that pooled it.
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Who cites it
122 citing papers in PubMed, 3 syntheses or guidelines pooled it, 170 citations in OpenAlex.
- Pooled it
- C-reactive protein as an effector molecule in Covid-19 pathogenesis.Reviews in medical virology · 2021Pooled it
- Severe acute respiratory syndrome coronavirus 2 and renin-angiotensin system blockers: A review and pooled analysis.Archives of cardiovascular diseases · 2020Pooled it
- METTL3 mediates mJournal of advanced research · 2026Article
- Sex-Specific Exosome Cargo Reveals Potential New Mechanisms of Salt-Sensitive Hypertension.Hypertension (Dallas, Tex. : 1979) · 2026Article
- Microglial activation and RAS signaling: a dual-edged sword in neuroinflammation.American journal of physiology. Regulatory, integrative and comparative physiology · 2026Review
- ADAM17 Supports Disinhibition of Pre-sympathetic Glutamatergic Neurons Through Microglial Chemotaxis.Neuroscience bulletin · 2026Article
- Targeting Kinin B1R Attenuates Hypertension Through AT1R-Dependent Mechanisms.Circulation research · 2025Article
- Molecular dissection of the role of ACE2 in glucose homeostasis.Physiological reviews · 2025Review
- Novel insights into the central protective role of ACE2 in diabetic cardiomyopathy: from underlying signaling pathways to therapeutic perspectives.Molecular and cellular biochemistry · 2025Review
- ADAM17 as a promising therapeutic target: from structural basis to inhibitor discovery in human diseases.Frontiers in pharmacology · 2025Review
- UBR1 Promotes Sex-Dependent ACE2 Ubiquitination in Hypertension.Hypertension (Dallas, Tex. : 1979) · 2025Article
- Antiviral effects of mogroside V against porcine reproductive and respiratory syndrome virusFrontiers in microbiology · 2025Article
- Angiotensin-Converting Enzyme 2 Posttranslational Modifications and Implications for Hypertension and SARS-CoV-2: 2023 Lewis K. Dahl Memorial Lecture.Hypertension (Dallas, Tex. : 1979) · 2024Review
- SARS-CoV-2 Spike Protein Enhances Carboxypeptidase Activity of Angiotensin-Converting Enzyme 2.International journal of molecular sciences · 2024Article
- Physiology of Vitamin D-Focusing on Disease Prevention.Nutrients · 2024Review
- Obese Male Mice Exposed to Early Life Stress Display Sympathetic Activation and Hypertension Independent of Circulating Angiotensin II.Journal of the American Heart Association · 2024Article
- Cardiovascular dysfunction induced by combined exposure to nicotine inhalation and high-fat diet.American journal of physiology. Heart and circulatory physiology · 2024Article
- New Approaches Targeting the Renin-Angiotensin System: Inhibition of Brain Aminopeptidase A, ACE2 Ubiquitination, and Angiotensinogen.The Canadian journal of cardiology · 2023Review
- CircHIPK2 facilitates phenotypic switching of vascular smooth muscle cells in hypertension.Journal of human hypertension · 2023Article
62 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
rationaleNeurogenic hypertension is characterized by an increase in sympathetic activity and often resistance to drug treatments. We previously reported that it is also associated with a reduction of angiotensin-converting enzyme type 2 (ACE2) and an increase in a disintegrin and metalloprotease 17 (ADAM17) activity in experimental hypertension. In addition, while multiple cells within the central nervous system have been involved in the development of neurogenic hypertension, the contribution of ADAM17 has not been investigated.
objectiveTo assess the clinical relevance of this ADAM17-mediated ACE2 shedding in hypertensive patients and further identify the cell types and signaling pathways involved in this process. METHODS AND
resultsUsing a mass spectrometry-based assay, we identified ACE2 as the main enzyme converting angiotensin II into angiotensin-(1-7) in human cerebrospinal fluid. We also observed an increase in ACE2 activity in the cerebrospinal fluid of hypertensive patients, which was correlated with systolic blood pressure. Moreover, the increased level of tumor necrosis factor-α in those cerebrospinal fluid samples confirmed that ADAM17 was upregulated in the brain of hypertensive patients. To further assess the interaction between brain renin-angiotensin system and ADAM17, we generated mice lacking angiotensin II type 1 receptors specifically on neurons. Our data reveal that despite expression on astrocytes and other cells types in the brain, ADAM17 upregulation during deoxycorticosterone acetate-salt hypertension occurs selectively on neurons, and neuronal angiotensin II type 1 receptors are indispensable to this process. Mechanistically, reactive oxygen species and extracellular signal-regulated kinase were found to mediate ADAM17 activation.
conclusionsOur data demonstrate that angiotensin II type 1 receptors promote ADAM17-mediated ACE2 shedding in the brain of hypertensive patients, leading to a loss in compensatory activity during neurogenic hypertension.
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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.