ArticleArteriosclerosis, thrombosis, and vascular biology2016
Hypoxia-Inducible Factor 1α Is a Critical Downstream Mediator for Hypoxia-Induced Mitogenic Factor (FIZZ1/RELMα)-Induced Pulmonary Hypertension.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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43 citing papers in PubMed, 63 citations in OpenAlex.
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- Novel insights and new therapeutic potentials for macrophages in pulmonary hypertension.Respiratory research · 2024Review
- Adipokines in pulmonary hypertension: angels or demons?Heliyon · 2023Review
- Resistin-like Molecule α and Pulmonary Vascular Remodeling: A Multi-Strain Murine Model of Antigen and Urban Ambient Particulate Matter Co-Exposure.International journal of molecular sciences · 2023Article
- Endotyping COPD: hypoxia-inducible factor-2 as a molecular "switch" between the vascular and airway phenotypes?European respiratory review : an official journal of the European Respiratory Society · 2023Review
- 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
- Pulmonary Vascular Remodeling in Pulmonary Hypertension.Journal of personalized medicine · 2023Review
- Resistin-like molecules: a marker, mediator and therapeutic target for multiple diseases.Cell communication and signaling : CCS · 2023Review
- Modulation of CaHandbook of experimental pharmacology · 2023Article
- Inflammation and immunity in the pathogenesis of hypoxic pulmonary hypertension.Frontiers in immunology · 2023Review
- Identification of exercise-regulated genes in mice exposed to cigarette smoke.Physiological reports · 2022Article
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8 authors at 1 institution in 2 countries.
Funding
Abstract
objectivePulmonary hypertension (PH) is characterized by progressive elevation of pulmonary vascular resistance, right ventricular failure, and ultimately death. We have shown that in rodents, hypoxia-induced mitogenic factor (HIMF; also known as FIZZ1 or resistin-like molecule-β) causes PH by initiating lung vascular inflammation. We hypothesized that hypoxia-inducible factor-1 (HIF-1) is a critical downstream signal mediator of HIMF during PH development. APPROACH AND
resultsIn this study, we compared the degree of HIMF-induced pulmonary vascular remodeling and PH development in wild-type (HIF-1α(+/+)) and HIF-1α heterozygous null (HIF-1α(+/-)) mice. HIMF-induced PH was significantly diminished in HIF-1α(+/-) mice and was accompanied by a dysregulated vascular endothelial growth factor-A-vascular endothelial growth factor receptor 2 pathway. HIF-1α was critical for bone marrow-derived cell migration and vascular tube formation in response to HIMF. Furthermore, HIMF and its human homolog, resistin-like molecule-β, significantly increased interleukin (IL)-6 in macrophages and lung resident cells through a mechanism dependent on HIF-1α and, at least to some extent, on nuclear factor κB.
conclusionsOur results suggest that HIF-1α is a critical downstream transcription factor for HIMF-induced pulmonary vascular remodeling and PH development. Importantly, both HIMF and human resistin-like molecule-β significantly increased IL-6 in lung resident cells and increased perivascular accumulation of IL-6-expressing macrophages in the lungs of mice. These data suggest that HIMF can induce HIF-1, vascular endothelial growth factor-A, and interleukin-6, which are critical mediators of both hypoxic inflammation and PH pathophysiology.
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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.