ArticleHypertension (Dallas, Tex. : 1979)2019
ACE2 and ADAM17 Interaction Regulates the Activity of Presympathetic Neurons.
Article in Hypertension (Dallas, Tex. : 1979), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 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
65 citing papers in PubMed, 1 synthesis or guideline pooled it, 94 citations in OpenAlex.
- The rationale for the treatment of long-Covid symptoms - A cardiologist's view.Frontiers in cardiovascular medicine · 2022Pooled it
- Co-ultramicronized palmitoylethanolamide/luteolin normalizes GABAClinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology · 2023Trial
- The ADAM Family of Proteases: Structure, Substrates, and Roles in Liver Diseases.International journal of molecular sciences · 2026Review
- ADAM17 Supports Disinhibition of Pre-sympathetic Glutamatergic Neurons Through Microglial Chemotaxis.Neuroscience bulletin · 2026Article
- Altered Bilateral Motor Cortex Excitability and Peripheral Glutamate/GABA Imbalance in Generalized Anxiety Disorder: A TMS Investigation.Psychology research and behavior management · 2026Article
- Engineered Liposomal Delivery ofPharmaceutics · 2025Article
- Angiotensin-Converting Enzyme-2 (ACE2) Downregulation During Coronavirus Infection.Molecular biotechnology · 2025Review
- Molecular dissection of the role of ACE2 in glucose homeostasis.Physiological reviews · 2025Review
- Expression of SARS-CoV-2 entry receptor ACE2 in human brain and its association with Alzheimer's disease and COVID-19.Molecular psychiatry · 2025Review
- Food-Derived Up-Regulators and Activators of Angiotensin Converting Enzyme 2: A Review.Journal of agricultural and food chemistry · 2024Review
- The possible mechanism and research progress of ACE2 involved in cardiovascular injury caused by COVID-19: a review.Frontiers in cardiovascular medicine · 2024Review
- New Approaches Targeting the Renin-Angiotensin System: Inhibition of Brain Aminopeptidase A, ACE2 Ubiquitination, and Angiotensinogen.The Canadian journal of cardiology · 2023Review
- Nedd4-2 up-regulation is associated with ACE2 ubiquitination in hypertension.Cardiovascular research · 2023Article
- Lowered Delta Activity in Post-COVID-19 Patients with Fatigue and Cognitive Impairment.Biomedicines · 2023Article
- P38 MAPK activated ADAM17 mediates ACE2 shedding and promotes cardiac remodeling and heart failure after myocardial infarction.Cell communication and signaling : CCS · 2023Article
- Investigating the possible mechanisms of autonomic dysfunction post-COVID-19.Autonomic neuroscience : basic & clinical · 2023Review
- SARS-CoV-2 and Hypertension: Evidence Supporting Invasion into the Brain Via Baroreflex Circuitry and the Role of Imbalanced Renin-Angiotensin-Aldosterone-System.Neuroscience insights · 2023Article
- Prevalence and patterns of symptoms of dysautonomia in patients with long-COVID syndrome: A cross-sectional study.Annals of clinical and translational neurology · 2022Article
- The ACE2 Receptor for Coronavirus Entry Is Localized at Apical Cell-Cell Junctions of Epithelial Cells.Cells · 2022Article
- Article
5 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Brain renin angiotensin system within the paraventricular nucleus plays a critical role in balancing excitatory and inhibitory inputs to modulate sympathetic output and blood pressure regulation. We previously identified ACE2 and ADAM17 as a compensatory enzyme and a sheddase, respectively, involved in brain renin angiotensin system regulation. Here, we investigated the opposing contribution of ACE2 and ADAM17 to hypothalamic presympathetic activity and ultimately neurogenic hypertension. New mouse models were generated where ACE2 and ADAM17 were selectively knocked down from all neurons (AC-N) or Sim1 neurons (SAT), respectively. Neuronal ACE2 deletion revealed a reduction of inhibitory inputs to AC-N presympathetic neurons relevant to blood pressure regulation. Primary neuron cultures confirmed ACE2 expression on GABAergic neurons synapsing onto excitatory neurons within the hypothalamus but not on glutamatergic neurons. ADAM17 expression was shown to colocalize with angiotensin-II type 1 receptors on Sim1 neurons, and the pressor relevance of this neuronal population was demonstrated by photoactivation. Selective knockdown of ADAM17 was associated with a reduction of FosB gene expression, increased vagal tone, and prevented the acute pressor response to centrally administered angiotensin-II. Chronically, SAT mice exhibited a blunted blood pressure elevation and preserved ACE2 activity during development of salt-sensitive hypertension. Bicuculline injection in those models confirmed the supporting role of ACE2 on GABAergic tone to the paraventricular nucleus. Together, our study demonstrates the contrasting impact of ACE2 and ADAM17 on neuronal excitability of presympathetic neurons within the paraventricular nucleus and the consequences of this mutual regulation in the context of 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.