ArticleHypertension (Dallas, Tex. : 1979)2013
Angiotensin-converting enzyme 2 priming enhances the function of endothelial progenitor cells and their therapeutic efficacy.
Article in Hypertension (Dallas, Tex. : 1979), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 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.
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Who cites it
62 citing papers in PubMed, 102 citations in OpenAlex.
- Trial
- From Cerebrovascular Injury to Vascular Cognitive Impairment and Dementia: Therapeutic Potential of Stem Cell-Derived Extracellular Vesicles.Biomedicines · 2026Review
- Exercise-Intervened Endothelial Progenitor Cell Exosomes Protect N2a Cells by Improving Mitochondrial Function.International journal of molecular sciences · 2024Article
- The Immunomodulatory effect of exosomes in diabetes: a novel and attractive therapeutic tool in diabetes therapy.Frontiers in immunology · 2024Review
- The miR-210 Primed Endothelial Progenitor Cell Exosomes Alleviate Acute Ischemic Brain Injury.Current stem cell research & therapy · 2024Article
- MiR-17-5p Mediates the Effects of ACE2-Enriched Endothelial Progenitor Cell-Derived Exosomes on Ameliorating Cerebral Ischemic Injury in Aged Mice.Molecular neurobiology · 2023Article
- Enrichment of miR-17-5p enhances the protective effects of EPC-EXs on vascular and skeletal muscle injury in a diabetic hind limb ischemia model.Biological research · 2023Article
- Counter-regulatory renin-angiotensin system in hypertension: Review and update in the era of COVID-19 pandemic.Biochemical pharmacology · 2023Review
- Angiotensin-converting enzyme - human amniotic mesenchymal stem cells improve pulmonary vascular remodeling in rats with pulmonary hypertension by promoting angiogenesis and counteracting inflammation.International journal of clinical and experimental pathology · 2023Article
- The protective effects of miR-210 modified endothelial progenitor cells released exosomes in hypoxia/reoxygenation injured neurons.Experimental neurology · 2022Article
- Rab27a-dependent exosomes protect against cerebral ischemic injury by reducing endothelial oxidative stress and apoptosis.CNS neuroscience & therapeutics · 2022Article
- Fractional exhaled Nitric Oxide (FeNO) level as a predictor of COVID-19 disease severity.Nitric oxide : biology and chemistry · 2022Article
- EPC-EXs improve astrocyte survival and oxidative stress through different uptaking pathways in diabetic hypoxia condition.Stem cell research & therapy · 2022Article
- Compromised endothelial progenitor cell exosomal communication with endothelial cells in hypertension ischemia conditions.Frontiers in stroke · 2022Article
- Neurological complications and infection mechanism of SARS-COV-2.Signal transduction and targeted therapy · 2021Review
- The SARS-CoV-2/Receptor Axis in Heart and Blood Vessels: A Crisp Update on COVID-19 Disease with Cardiovascular Complications.Viruses · 2021Review
- COVID-19 and stroke: A review.Brain hemorrhages · 2021Review
- Changes of coagulation function and risk of stroke in patients with COVID-19.Brain and behavior · 2021Article
- Pathophysiologic mechanisms of cerebral endotheliopathy and stroke due to Sars-CoV-2.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021Review
- Multifunctional angiotensin converting enzyme 2, the SARS-CoV-2 entry receptor, and critical appraisal of its role in acute lung injury.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2021Review
2 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Angiotensin-converting enzyme 2 (ACE2) is a lately discovered enzyme catalyzing Angiotensin II into Angiotensin 1-7. Angiotensin II has been reported to impair endothelial progenitor cell (EPC) function and is detrimental to stroke. Here, we studied the role of ACE2 in regulating EPC function in vitro and in vivo. EPCs were cultured from human renin and angiotensinogen transgenic (R+A+) mice and their controls (R-A-). In in vitro experiments, EPCs were transduced with lentivirus-ACE2 or lentivirus-green fluorescence protein. The effects of ACE2 overexpression on EPC function and endothelial NO synthase (eNOS)/nicotinamide adenine dinucleotide phosphate oxidase (Nox) expression were determined. ACE2, eNOS, and Nox inhibitors were used for pathway validation. In in vivo studies, the therapeutic efficacy of EPCs overexpressing ACE2 was determined at day 7 after ischemic stroke induced by middle cerebral artery occlusion. We found that (1) lentivirus-ACE2 transduction resulted in a 4-fold increase of ACE2 expression in EPCs. This was accompanied with an increase in eNOS expression and NO production, and a decrease in Nox2 and -4 expression and reactive oxygen species production. (2) ACE2 overexpression improved the abilities of EPC migration and tube formation, which were impaired in R+A+ mice. These effects were inhibited by ACE2 or eNOS inhibitor and further enhanced by Nox inhibitor. (3) Transfusion of lentivirus-ACE2-primed EPCs reduced cerebral infarct volume and neurological deficits, and increased cerebral microvascular density and angiogenesis. Our data demonstrate that ACE2 improves EPC function, via regulating eNOS and Nox pathways, and enhances the efficacy of EPC-based therapy for ischemic stroke.
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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.