ArticleJournal of translational medicine2015
Deletion of angiotensin-converting enzyme 2 exacerbates renal inflammation and injury in apolipoprotein E-deficient mice through modulation of the nephrin and TNF-alpha-TNFRSF1A signaling.
Article in Journal of translational medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04331470 (Evaluation of Efficacy of Pharmacotherapy Treatment of COVID- 19 Infection Using Oral Levamisole and Formoterol+Budesonide Inhaler and Comparison of This Treatment Protocol With Standard National Treatment of the Disease), which is not on this map. Cited by 21 papers.
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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.
Evaluation of Efficacy of Pharmacotherapy Treatment of COVID- 19 Infection Using Oral Levamisole and Formoterol+Budesonide Inhaler and Comparison of This Treatment Protocol With Standard National Treatment of the Disease
Who cites it
21 citing papers in PubMed, 44 citations in OpenAlex.
- Integrating bulk and single-cell transcriptome profiling to uncover diagnostic biomarkers and regulatory mechanisms of oxidative stress in spinal cord injury.Neural regeneration research · 2026Article
- Targeting the renin-angiotensin system in sepsis-associated AKI: from pathophysiology to precision medicine.Frontiers in immunology · 2026Review
- Telomere Dysfunction in Renal Tubular Epithelial Cells Leads to Kidney Fibrosis.Journal of the American Society of Nephrology : JASN · 2025Article
- The COVID-19 pandemic and Alzheimer's disease: mutual risks and mechanisms.Translational neurodegeneration · 2022Review
- Functional ACE2 deficiency leading to angiotensin imbalance in the pathophysiology of COVID-19.Reviews in endocrine & metabolic disorders · 2022Review
- Well-differentiated liver cancers reveal the potential link between ACE2 dysfunction and metabolic breakdown.Scientific reports · 2022Article
- Foe and friend in the COVID-19-associated acute kidney injury: an insight on intrarenal renin-angiotensin system.Acta biochimica et biophysica Sinica · 2022Review
- Mechanisms of COVID-19-induced kidney injury and current pharmacotherapies.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2022Review
- Experimental Study on the Mechanism of Cinnamaldehyde Ameliorate Proteinuria Induced by Adriamycin.BioMed research international · 2022Article
- Single Cell Dissection of Epithelial-Immune Cellular Interplay in Acute Kidney Injury Microenvironment.Frontiers in immunology · 2022Article
- Abnormal apelin-ACE2 and SGLT2 signaling contribute to adverse cardiorenal injury in patients with COVID-19.International journal of cardiology · 2021Article
- Article
- Novel ACE2 protein interactions relevant to COVID-19 predicted by evolutionary rate correlations.PeerJ · 2021Article
- Reduced urinary levels of angiotensin-converting enzyme 2 activity predict acute kidney injury in critically ill patients.Critical care and resuscitation : journal of the Australasian Academy of Critical Care Medicine · 2020Article
- The ACE2-deficient mouse: A model for a cytokine storm-driven inflammation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- The COVID-19 outbreak and the angiotensin-converting enzyme 2: too little or too much?Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2020Article
- SARS-CoV-2 and Other Respiratory Viruses: What Does Oxidative Stress Have to Do with It?Oxidative medicine and cellular longevity · 2020Review
- Classic and Nonclassic Renin-Angiotensin Systems in the Critically Ill.Critical care clinics · 2019Review
- Long-term renal sympathetic denervation ameliorates renal fibrosis and delays the onset of hypertension in spontaneously hypertensive rats.American journal of translational research · 2018Article
- Intrarenal Angiotensin-Converting Enzyme: the Old and the New.Current hypertension reports · 2017Review
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe renin-angiotensin system (RAS) has been implicated in atherosclerotic lesions and progression to chronic kidney diseases. We examined regulatory roles of angiotensin-converting enzyme 2 (ACE2) in the apolipoprotein E (ApoE) knockout (KO) kidneys.
methodsThe 3-month-old wild-type, ApoEKO, ACE2KO and ApoE/ACE2 double-KO (DKO) mice in a C57BL/6 background were used. The ApoEKO mice were randomized to daily deliver either Ang II (1.5 mg/kg) and/or human recombinant ACE2 (rhACE2; 2 mg/kg) for 2 weeks. We examined changes in pro-inflammatory cytokines, renal ultrastructure, and pathological signaling in mouse kidneys.
resultsDownregulation of ACE2 and nephrin levels was observed in ApoEKO kidneys. Genetic ACE2 deletion resulted in modest elevations in systolic blood pressure levels and Ang II type 1 receptor expression and reduced nephrin expression in kidneys of the ApoE/ACE2 DKO mice with a decrease in renal Ang-(1-7) levels. These changes were linked with marked increases in renal superoxide generation, NADPH oxidase (NOX) 4 and proinflammatory factors levels, including interleukin (IL)-1beta, IL-6, IL-17A, RANTES, ICAM-1, Tumor necrosis factor-alpha (TNF-alpha) and TNFRSF1A. Renal dysfunction and ultrastructure injury were aggravated in the ApoE/ACE2 DKO mice and Ang II-infused ApoEKO mice with increased plasma levels of creatinine, blood urea nitrogen and enhanced levels of Ang II in plasma and kidneys. The Ang II-mediated reductions of renal ACE2 and nephrin levels in ApoEKO mice were remarkably rescued by rhACE2 supplementation, along with augmentation of renal Ang-(1-7) levels. More importantly, rhACE2 treatment significantly reversed Ang II-induced renal inflammation, superoxide generation, kidney dysfunction and adverse renal injury in ApoEKO mice with suppression of the NOX4 and TNF-alpha-TNFRSF1A signaling. However, rhACE2 had no effect on renal NOX2 and TNFRSF1B expression and circulating lipid levels.
conclusionsACE2 deficiency exacerbates kidney inflammation, oxidative stress and adverse renal injury in the ApoE-mutant mice through modulation of the nephrin, NOX4 and TNF-alpha-TNFRSF1A signaling. While rhACE2 supplementation alleviates inflammation, renal dysfunction and glomerulus injury in the ApoE-mutant mice associated with upregulations of Ang-(1-7) levels and nephrin expression and suppression of the TNF-alpha-TNFRSF1A signaling. Strategies aimed at enhancing the ACE2/Ang-(1-7) actions may have important therapeutic potential for atherosclerotic renal injury and kidney diseases.
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