ArticleHypertension (Dallas, Tex. : 1979)2020
Gut Pathology and Its Rescue by ACE2 (Angiotensin-Converting Enzyme 2) in Hypoxia-Induced Pulmonary Hypertension.
Article in Hypertension (Dallas, Tex. : 1979), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 47 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
47 citing papers in PubMed, 68 citations in OpenAlex.
- Beyond the Heart-Lung Axis: A Review of the Crosstalk Between the Hemodynamic, Neurohormonal, and Immune Systems in Pulmonary Hypertension.Comprehensive physiology · 2026Review
- Salidroside and mesenchymal stem cells alleviate hypobaric hypoxia-induced lung injury and are associated with alterations in the gut-lung axis.Biochemistry and biophysics reports · 2026Article
- Reduction in microbiota-derived short-chain fatty acids contributes to the pathogenesis of pulmonary arterial hypertension.Respiratory research · 2026Article
- Gut-Heart Axis in Myocardial Repair: Mechanisms, Cross-Organ Networks, and Therapeutic Opportunities.Circulation research · 2026Review
- Morning Larks and Night Owls: Considering Chronotype in Evaluation of Patients with Pulmonary Hypertension.Annals of the American Thoracic Society · 2026Article
- Tryptophan metabolism: a potential link between the gut microbiota and pulmonary vascular remodeling in pulmonary hypertension.Frontiers in cellular and infection microbiology · 2026Review
- Circadian clock-gut microbiota axis in pulmonary hypertension: linking gut-lung crosstalk, immune timing and vascular remodeling.Frontiers in physiology · 2026Review
- Microbiome Dysregulation and Inflammation: Key Players in Pulmonary Hypertension Pathophysiology.Biomedicines · 2025Article
- Article
- Gut Microbiome in Pulmonary Arterial Hypertension-An Emerging Frontier.Infectious disease reports · 2025Review
- Leukotrienes: Bridging the Inflammatory Gap in Asthma and Inflammatory Bowel Diseases (IBD).Comprehensive Physiology · 2025Review
- Gut-X axis.iMeta · 2025Review
- Geniposide Protects Against Myocardial Infarction Injury via the Restoration in Gut Microbiota and Gut-Brain Axis.Journal of cellular and molecular medicine · 2025Article
- The gut-lung axis: effects and mechanisms of gut microbiota on pulmonary diseases.Frontiers in immunology · 2025Review
- Oral administration of pioglitazone inhibits pulmonary hypertension by regulating the gut microbiome and plasma metabolome in male rats.Physiological reports · 2025Article
- Promising dawn in the management of pulmonary hypertension: The mystery veil of gut microbiota.iMeta · 2024Review
- Immune regulation of the gut-brain axis and lung-brain axis involved in ischemic stroke.Neural regeneration research · 2024Review
- Pulmonary Hypertension and the Gut Microbiome.Biomedicines · 2024Review
- Stress and the gut-brain axis: an inflammatory perspective.Frontiers in molecular neuroscience · 2024Review
- Effects of the ACE2-Ang-(1-7)-Mas axis on gut flora diversity and intestinal metabolites in SuHx mice.Frontiers in microbiology · 2024Article
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
15 authors at 3 institutions in 4 countries.
Funding
Abstract
Therapeutic advances for pulmonary hypertension (PH) have been incremental because of the focus on the pulmonary vasculature in PH pathology. Here, we evaluate the concept that PH is, rather, a systemic disorder involving interplay among multiorgan systems, including brain, gut, and lungs. Therefore, the objective of this study was to evaluate the hypothesis that PH is associated with a dysfunctional brain-gut-lung axis and that global overexpression of ACE2 (angiotensin-converting enzyme 2) rebalances this axis and protects against PH. ACE2 knockin and wild-type (WT; C57BL/6) mice were subjected to chronic hypoxia (10% FIO2) or room air for 4 weeks. Cardiopulmonary hemodynamics, histology, immunohistochemistry, and fecal 16S rRNA microbial gene analyses were evaluated. Hypoxia significantly increased right ventricular systolic pressure, sympathetic activity as well as the number and activation of microglia in the paraventricular nucleus of the hypothalamus in WT mice. This was associated with a significant increase in muscularis layer thickening and decreases in both villi length and goblet cells and altered gut microbiota. Global overexpression of ACE2 prevented changes in hypoxia-induced pulmonary and gut pathophysiology and established distinct microbial communities from WT hypoxia mice. Furthermore, WT mice subjected to fecal matter transfer from ACE2 knockin mice were resistant to hypoxia-induced PH compared with their controls receiving WT fecal matter transfer. These observations demonstrate that ACE2 ameliorates these hypoxia-induced pathologies and attenuates PH. The data implicate dysfunctional brain-gut-lung communication in PH and provide novel avenues for therapeutic interventions.
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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.