ArticleAmerican journal of physiology. Lung cellular and molecular physiology2014
Hypoxia-induced mitogenic factor (FIZZ1/RELMα) induces endothelial cell apoptosis and subsequent interleukin-4-dependent pulmonary hypertension.
Article in American journal of physiology. Lung cellular and molecular physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 66 citations in OpenAlex.
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- Article
- Context-dependent roles of resistin-like molecule β in mucosal defense and inflammatory diseases.Frontiers in immunology · 2026Review
- Plasma IL4 Levels Linked to Pulmonary Hypertension Severity and Outcome.Clinical and experimental pharmacology & physiology · 2025Observational
- Changes in Macrophages in Pulmonary Hypertension: A Focus on High-altitude Pulmonary Hypertension.Anatolian journal of cardiology · 2025Review
- STAT6 deficiency mitigates the severity of pulmonary arterial hypertension caused by chronic intermittent hypoxia by suppressing Th2-inducing cytokines.Respiratory research · 2025Article
- Therapeutic challenges and new therapeutic targets for combined capillary pulmonary hypertension: a review.Frontiers in medicine · 2025Review
- The role of vasculature and angiogenesis in respiratory diseases.Angiogenesis · 2024Review
- In the Search for Biomarkers of Pulmonary Arterial Hypertension, Are Cytokines IL-2, IL-4, IL-6, IL-10, and IFN-Gamma the Right Indicators to Use?International journal of molecular sciences · 2023Article
- Human Resistin Induces Cardiac Dysfunction in Pulmonary Hypertension.Journal of the American Heart Association · 2023Article
- Distinctive Signs of Disease as Deterrents for the Endothelial Function: A Systematic Review.Metabolites · 2023Review
- Endothelial cell ferroptosis mediates monocrotaline-induced pulmonary hypertension in rats by modulating NLRP3 inflammasome activation.Scientific reports · 2022Article
- Interrelationship and Sequencing of Interleukins4, 13, 31, and 33 - An Integrated Systematic Review: Dermatological and Multidisciplinary Perspectives.Journal of inflammation research · 2022Review
- Endothelial cells in the pathogenesis of pulmonary arterial hypertension.The European respiratory journal · 2021Review
- Role of the Immune System Elements in Pulmonary Arterial Hypertension.Journal of clinical medicine · 2021Review
- The inflammatory role of dysregulated IRS2 in pulmonary vascular remodeling under hypoxic conditions.American journal of physiology. Lung cellular and molecular physiology · 2021Article
- Resistin-like molecule β acts as a mitogenic factor in hypoxic pulmonary hypertension via the CaRespiratory research · 2021Article
- Hypoxia-Induced Mitogenic Factor: A Multifunctional Protein Involved in Health and Disease.Frontiers in cell and developmental biology · 2021Review
- Resistin-Like Molecule α Dysregulates Cardiac Bioenergetics in Neonatal Rat Cardiomyocytes.Frontiers in cardiovascular medicine · 2021Article
- Cytokines, Chemokines, and Inflammation in Pulmonary Arterial Hypertension.Advances in experimental medicine and biology · 2021Article
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Authors and funding
8 authors at 1 institution in 1 country.
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Abstract
Pulmonary hypertension (PH) is characterized by elevated pulmonary artery pressure that leads to progressive right heart failure and ultimately death. Injury to endothelium and consequent wound repair cascades have been suggested to trigger pulmonary vascular remodeling, such as that observed during PH. The relationship between injury to endothelium and disease pathogenesis in this disorder remains poorly understood. We and others have shown that, in mice, hypoxia-induced mitogenic factor (HIMF, also known as FIZZ1 or RELMα) plays a critical role in the pathogenesis of lung inflammation and the development of PH. In this study, we dissected the mechanism by which HIMF and its human homolog resistin (hRETN) induce pulmonary endothelial cell (EC) apoptosis and subsequent lung inflammation-mediated PH, which exhibits many of the hallmarks of the human disease. Systemic administration of HIMF caused increases in EC apoptosis and interleukin (IL)-4-dependent vascular inflammatory marker expression in mouse lung during the early inflammation phase. In vitro, HIMF, hRETN, and IL-4 activated pulmonary microvascular ECs (PMVECs) by increasing angiopoietin-2 expression and induced PMVEC apoptosis. In addition, the conditioned medium from hRETN-treated ECs had elevated levels of endothelin-1 and caused significant increases in pulmonary vascular smooth muscle cell proliferation. Last, HIMF treatment caused development of PH that was characterized by pulmonary vascular remodeling and right heart failure in wild-type mice but not in IL-4 knockout mice. These data suggest that HIMF contributes to activation of vascular inflammation at least in part by inducing EC apoptosis in the lung. These events lead to subsequent PH.
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