ArticlePloS one2012
The acute phase reactant orosomucoid-1 is a bimodal regulator of angiogenesis with time- and context-dependent inhibitory and stimulatory properties.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 60 citations in OpenAlex.
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- Acute Phase Protein Orosomucoid (Alpha-1-Acid Glycoprotein) Predicts Delayed Cerebral Ischemia and 3-Month Unfavorable Outcome after Aneurysmal Subarachnoid Hemorrhage.International journal of molecular sciences · 2023Article
- Orosomucoid 1 promotes colorectal cancer progression and liver metastasis by affecting PI3K/AKT pathway and inducing macrophage M2 polarization.Scientific reports · 2023Article
- Sportomics method to assess acute phase proteins in Olympic level athletes using dried blood spots and multiplex assay.Scientific reports · 2022Article
- ORM 1 as a biomarker of increased vascular invasion and decreased sorafenib sensitivity in hepatocellular carcinoma.Bosnian journal of basic medical sciences · 2022Article
- Glioblastoma microenvironment contains multiple hormonal and non-hormonal growth-stimulating factors.Fluids and barriers of the CNS · 2022Article
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- Cardiac Adipose Tissue Contributes to Cardiac Repair: a Review.Stem cell reviews and reports · 2021Review
- miR-362-3p Targets Orosomucoid 1 to Promote Cell Proliferation, Restrain Cell Apoptosis and Thereby Mitigate Hypoxia/Reoxygenation-Induced Cardiomyocytes Injury.Cardiovascular toxicology · 2021Article
- Ozone-induced acute phase response in lung versus liver: the role of adrenal-derived stress hormones.Journal of toxicology and environmental health. Part A · 2021Article
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- Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundTissues respond to injury by releasing acute phase reaction (APR) proteins which regulate inflammation and angiogenesis. Among the genes upregulated in wounded tissues are tumor necrosis factor-alpha (TNFα) and the acute phase reactant orosomucoid-1 (ORM1). ORM1 has been shown to modulate the response of immune cells to TNFα, but its role on injury- and TNFα-induced angiogenesis has not been investigated. This study was designed to characterize the role of ORM1 in the angiogenic response to injury and TNFα. METHODS AND
resultsAngiogenesis was studied with in vitro, ex vivo, and in vivo angiogenesis assays. Injured rat aortic rings cultured in collagen gels produced an angiogenic response driven by macrophage-derived TNFα. Microarray analysis and qRT-PCR showed that TNFα and ORM1 were upregulated prior to angiogenic sprouting. Exogenous ORM1 delayed the angiogenic response to injury and inhibited the proangiogenic effect of TNFα in cultures of aortic rings or isolated endothelial cells, but stimulated aortic angiogenesis over time while promoting VEGF production and activity. ORM1 inhibited injury- and TNFα-induced phosphorylation of MEK1/2 and p38 MAPK in aortic rings, but not of NFκB. This effect was injury/TNFα-specific since ORM1 did not inhibit VEGF-induced signaling, and cell-specific since ORM1 inhibited TNFα-induced phosphorylation of MEK1/2 and p38 MAPK in macrophages and endothelial cells, but not mural cells. Experiments with specific inhibitors demonstrated that the MEK/ERK pathway was required for angiogenesis. ORM1 inhibited angiogenesis in a subcutaneous in vivo assay of aortic ring-induced angiogenesis, but stimulated developmental angiogenesis in the chorioallantoic membrane (CAM) assay.
conclusionORM1 regulates injury-induced angiogenesis in a time- and context-dependent manner by sequentially dampening the initial TNFα-induced angiogenic response and promoting the downstream stimulation of the angiogenic process by VEGF. The context-dependent nature of ORM1 angioregulatory function is further demonstrated in the CAM assay where ORM1 stimulates developmental angiogenesis without exerting any inhibitory activity.
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