ArticleAmerican journal of respiratory and critical care medicine2018
AMP-activated Protein Kinase Phosphorylation of Angiotensin-Converting Enzyme 2 in Endothelium Mitigates Pulmonary Hypertension.
Article in American journal of respiratory and critical care medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 129 papers, 2 of them syntheses that pooled it.
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129 citing papers in PubMed, 2 syntheses or guidelines pooled it, 184 citations in OpenAlex.
- Noninsulin-based antihyperglycemic medications in patients with diabetes and COVID-19: A systematic review and meta-analysis.Journal of diabetes · 2023 · on this mapPooled it
- Metformin in Patients With COVID-19: A Systematic Review and Meta-Analysis.Frontiers in medicine · 2021Pooled it
- Allosteric Interactions of Flavonoids with ACE2 and Potential Implications for COVID-19: Computational Insights, Metabolic and Mitochondrial Effects of Rutin in A549 Cells.Cell biochemistry and biophysics · 2026Article
- T1R3 Anchors ACE2 at the Pulmonary Endothelial Cell Surface to Attenuate Vascular Injury Following SARS-CoV-2 Spike 1 Protein Exposure In Vitro.Journal of cellular and molecular medicine · 2026Article
- Post-translational modification crosstalk in pulmonary arterial hypertension: mechanisms and therapeutic implications.Molecular biology reports · 2026Review
- Inhibition of SARS-CoV-2 spike S1-ACE2 binding interaction and downregulation of ACE2 gene expression by Malaysian stingless bee honey and its bioactive compound, stilbamidine (SDC).Molecular biology reports · 2026Article
- PAH-former: Transfer learning for efficient discovery of pulmonary arterial hypertension-associated genes.PloS one · 2026Article
- 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
- Effects of oral antidiabetic agents on the renin-angiotensin-aldosterone system.European journal of clinical pharmacology · 2025Review
- Shared genetic features inference among hypoxia-ischemia diseases in the presence of heterogenous omics data based on a novel risk assessment method.Frontiers in genetics · 2025Article
- Special Issue: "Enzymes and Enzyme Inhibitors-Applications in Medicine and Diagnosis 2.0".International journal of molecular sciences · 2024Article
- Metformin use and its association with various outcomes in COVID-19 patients with diabetes mellitus: a retrospective cohort study in a tertiary care facility.Annals of medicine · 2024Article
- Sivelestat protects against acute lung injury by up-regulating angiotensin-converting enzyme 2/angiotensin-(1-7)/Mas receptors.Journal of thoracic disease · 2024Article
- Fine-tuning AMPK in physiology and disease using point-mutant mouse models.Disease models & mechanisms · 2024Review
- 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
- SubSol-HIe is an AMPK-dependent hypoxia-responsive subnucleus of the nucleus tractus solitarius that coordinates the hypoxic ventilatory response and protects against apnoea in mice.Pflugers Archiv : European journal of physiology · 2024Article
- SARS-CoV-2 Spike Protein Enhances Carboxypeptidase Activity of Angiotensin-Converting Enzyme 2.International journal of molecular sciences · 2024Article
- 1-L Transcription of SARS-CoV-2 Spike Protein S1 Subunit.International journal of molecular sciences · 2024Article
- Endothelial HRedox biology · 2024Article
69 more citing papers are in PubMed but not listed here.
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22 authors at 6 institutions in 5 countries.
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Abstract
rationaleEndothelial dysfunction plays an integral role in pulmonary hypertension (PH). AMPK (AMP-activated protein kinase) and ACE2 (angiotensin-converting enzyme 2) are crucial in endothelial homeostasis. The mechanism by which AMPK regulates ACE2 in the pulmonary endothelium and its protective role in PH remain elusive.
objectivesWe investigated the role of AMPK phosphorylation of ACE2 Ser680 in ACE2 stability and deciphered the functional consequences of this post-translational modification of ACE2 in endothelial homeostasis and PH.
methodsBioinformatics prediction, kinase assay, and antibody against phospho-ACE2 Ser680 (p-ACE2 S680) were used to investigate AMPK phosphorylation of ACE2 Ser680 in endothelial cells. Using CRISPR-Cas9 genomic editing, we created gain-of-function ACE2 S680D knock-in and loss-of-function ACE2 knockout (ACE2 MEASUREMENTS AND MAIN
resultsPhosphorylation of ACE2 by AMPK enhanced the stability of ACE2, which increased Ang (angiotensin) 1-7 and endothelial nitric oxide synthase-derived NO bioavailability. ACE2 S680D knock-in mice were resistant to PH as compared with wild-type littermates. In contrast, ACE2-knockout mice exacerbated PH, a similar phenotype found in mice with endothelial cell-specific deletion of AMPKα2. Consistently, the concentrations of phosphorylated AMPK, p-ACE2 S680, and ACE2 were decreased in human lungs with idiopathic pulmonary arterial hypertension.
conclusionsImpaired phosphorylation of ACE2 Ser680 by AMPK in pulmonary endothelium leads to a labile ACE2 and hence is associated with the pathogenesis of PH. Thus, AMPK regulation of the vasoprotective ACE2 is a potential target for PH treatment.
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