Induction of angiogenesis by murine resistin: putative role of PI3-kinase and NO-dependent pathways
Abstract
Unlabelled Adipose tissue is a highly active endocrine organ, secreting bioactive molecules, adipokines, into the circulation. Obesity results in dysregulated adipokine secretion, contributing to pathophysiologies associated with this disorder, including insulin resistance and cardiovascular disease.Objectives To establish whether resistin, a novel bioactive molecule produced by murine adipose tissue, and implicated in insulin resistance in rodents, can induce angiogenic responses in aortic tissues and endothelial cells in vitro, and to investigate the signal transduction pathways involved in these responses.Results Recombinant murine resistin (5-100 ng ml(-1)) induced sprouting of cellular networks and migration from murine aortic arch explants, primary aortic endothelial cells and in a 'wound healing' model utilising murine b.End5 endothelioma cells. The increased migration and sprouting of endothelial cells, due to resistin, were blocked by wortmannin (100 nM) and LY294002 (10 microM), inhibitors of phosphatidylinositol-3-kinase (PI3K), and accompanied by PI3K-dependent phosphorylation of Akt; moreover, while the changes were not associated with altered production of nitric oxide (NO), resistin-induced angiogenic responses were inhibited by IKK Inhibitor X (5 microM), an inhibitor of activation of nuclear factor (NF)-kappaB.Conclusions Murine resistin induces endothelial cell migration and sprouting of cellular networks via a mechanism which appears dependent upon PI3K and NF-kappaB activity, but independent of altered NO production. Resistin may contribute to angiogenic responses sustaining adipose tissue expansion, or in arterial tissues distal to this site.
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Adipose tissue secretes several adipokines and endogenous angiogenesis inhibitors that modulate new blood vessel formation, including adiponectin, leptin, resistin, visfatin/thrombospondin 1, and plasminogen activator inhibitor.
“In addition to authentic angiogenic factors, AT secretes several important adipokines and endogenous angiogenesis inhibitors to modulate the balance of new blood vessel formation, including adiponectin (36,37), leptin (34), resistin (38), visfatin/thrombospondin 1 (39), and plasminogen activator inhibitor (40).”
From The ominous triad of adipose tissue dysfunction: inflammation, fibrosis, and impaired angiogenesis. (2017) · cites this paper as [38]
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The ominous triad of adipose tissue dysfunction: inflammation, fibrosis, and impaired angiogenesis.
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- Authors
- Robertson, S. A., Rae, C. J., & Graham, A.
- Affiliations
- Glasgow Caledonian University (GB)
- Corresponding author
- Graham, Annette
- Venue
- Regulatory Peptides
- Publisher
- Elsevier BV
- Published
- 2009-01
- Volume
- 152
- Issue
- 1-3
- Pages
- 41-47
- ISSN
- 0167-0115 (ISSN-L)
- OpenAlex
- W2084802277
- Cited by
- 35
- References
- 46
- Citations by year
- 2024: 1 · 2022: 1 · 2021: 2 · 2019: 1 · 2018: 2 · 2017: 3 · 2015: 6 · 2014: 1 · 2013: 6 · 2012: 4
- FWCI
- 1.98
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Regulatory Peptides (publishedVersion)
- PubMed (publishedVersion)
- ResearchOnline (acceptedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
- Funders
- Diabetes UK
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Keywords
- resistin, angiogenesis, endothelial cell migration, endothelial sprouting, PI3-kinase, Akt phosphorylation, NF-κB, nitric oxide, adipokines, adipose tissue, obesity, insulin resistance, wortmannin, LY294002, aortic endothelial cells, wound healing
- MeSH terms
- Animals, Cell Differentiation, Cell Movement, Cells, Cultured, Nitric Oxide, Phosphorylation, Recombinant Proteins, Signal Transduction, Neovascularization, Physiologic, Phosphatidylinositol 3-Kinases, Endothelial Cells, Mice, Resistin
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