ArticleJCI insight2021
Monocyte-released HERV-K dUTPase engages TLR4 and MCAM causing endothelial mesenchymal transition.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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The trial behind it
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Who cites it
28 citing papers in PubMed, 33 citations in OpenAlex.
- SNAI2/SLUG: a key regulator of endothelial-to-mesenchymal transition and vascular remodeling in cardiovascular diseases.Journal of cardiothoracic surgery · 2026Review
- Haemolytic injury and cardiovascular disease.Nature reviews. Cardiology · 2026Review
- The N‑Glycoproteomic Landscape of the Lung in Monocrotaline-Induced Pulmonary Arterial Hypertension.ACS omega · 2026Article
- BvrR From Brucella abortus Induces Neuroinflammation Through IRE1-Mediated Activation of ATF2 and NF-κB.MicrobiologyOpen · 2026Article
- Chronic Reactivation of Persistent Human Herpesviruses EBV, HHV-6 and VZV and Heightened Anti-dUTPase IgG Antibodies Are a Recurrent Hallmark in Post-Infectious ME/CFS and is Associated With Fatigue.Journal of medical virology · 2026Article
- Myeloid GPSM1 regulates atherosclerosis progression by governing monocyte and macrophage activation and chemotaxis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The Role of Toll-like Receptors and Viral Infections in the Pathogenesis and Progression of Pulmonary Arterial Hypertension-A Narrative Review.International journal of molecular sciences · 2025Review
- Human Endogenous Retroviruses and Diseases.MedComm · 2025Review
- Signaling pathways and targeted therapy for pulmonary hypertension.Signal transduction and targeted therapy · 2025Review
- New insights into pulmonary arterial hypertension: interaction between PANoptosis and perivascular inflammatory responses.Apoptosis : an international journal on programmed cell death · 2025Review
- Altered maturation and activation state of circulating monocytes is associated with their enhanced recruitment in pulmonary arterial hypertension.Respiratory research · 2025Article
- High Shear Stress Reduces ERG Causing Endothelial-Mesenchymal Transition and Pulmonary Arterial Hypertension.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Unlocking the Potential of Extracellular Vesicles in Cardiovascular Disease.Journal of cellular and molecular medicine · 2025Review
- Microbiome-Immune Interaction in Pulmonary Arterial Hypertension: What Have We Missed?Research (Washington, D.C.) · 2025Review
- Endogenous Retroviruses Unveiled: A Comprehensive Review of Inflammatory Signaling/Senescence-Related Pathways and Therapeutic Strategies.Aging and disease · 2024Review
- Single-Cell Imaging Maps Inflammatory Cell Subsets to Pulmonary Arterial Hypertension Vasculopathy.American journal of respiratory and critical care medicine · 2024Article
- The evaluation of human endogenous retroviral env expression in normal and cancerous tissues of the breast.Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences · 2024Article
- Endothelial-to-mesenchymal transition in tumour progression and its potential roles in tumour therapy.Annals of medicine · 2023Review
- Human Endogenous Retrovirus, SARS-CoV-2, and HIV Promote PAH via Inflammation and Growth Stimulation.International journal of molecular sciences · 2023Review
- Endogenous Retroviruses as Modulators of Innate Immunity.Pathogens (Basel, Switzerland) · 2023Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
We previously reported heightened expression of the human endogenous retroviral protein HERV-K deoxyuridine triphosphate nucleotidohydrolase (dUTPase) in circulating monocytes and pulmonary arterial (PA) adventitial macrophages of patients with PA hypertension (PAH). Furthermore, recombinant HERV-K dUTPase increased IL-6 in PA endothelial cells (PAECs) and caused pulmonary hypertension in rats. Here we show that monocytes overexpressing HERV-K dUTPase, as opposed to GFP, can release HERV-K dUTPase in extracellular vesicles (EVs) that cause pulmonary hypertension in mice in association with endothelial mesenchymal transition (EndMT) related to induction of SNAIL/SLUG and proinflammatory molecules IL-6 as well as VCAM1. In PAECs, HERV-K dUTPase requires TLR4-myeloid differentiation primary response-88 to increase IL-6 and SNAIL/SLUG, and HERV-K dUTPase interaction with melanoma cell adhesion molecule (MCAM) is necessary to upregulate VCAM1. TLR4 engagement induces p-p38 activation of NF-κB in addition to p-pSMAD3 required for SNAIL and pSTAT1 for IL-6. HERV-K dUTPase interaction with MCAM also induces p-p38 activation of NF-κB in addition to pERK1/2-activating transcription factor-2 (ATF2) to increase VCAM1. Thus in PAH, monocytes or macrophages can release HERV-K dUTPase in EVs, and HERV-K dUTPase can engage dual receptors and signaling pathways to subvert PAEC transcriptional machinery to induce EndMT and associated proinflammatory molecules.
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What OpenQuestion holds
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.