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Omentin reduces venous neointimal hyperplasia in arteriovenous fistula through hypoxia-inducible factor-1 alpha inhibition.
- Source :
-
Microvascular research [Microvasc Res] 2024 Jul; Vol. 154, pp. 104688. Date of Electronic Publication: 2024 Apr 18. - Publication Year :
- 2024
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Abstract
- Arteriovenous fistula (AVF) failure often involves venous neointimal hyperplasia (VNH) driven by elevated hypoxia-inducible factor-1 alpha (HIF-1α) in the venous wall. Omentin, known for its anti-inflammatory and anti-hyperplasia properties, has an uncertain role in early AVF failure. This study investigates omentin's impact on VNH using a chronic renal failure (CRF) rabbit model. The CRF rabbit model of AVF received omentin-expressing adenoviral vector or control β-gal vector to assess omentin's effects on VNH. Human vascular smooth muscle cells (HVSMCs), stimulated with tumor necrosis factor-α (TNF-α), were exposed to recombinant human omentin (Rh-OMT) to study its influence on cell proliferation and migration. The AMP-activated protein kinase (AMPK) inhibitor compound C and the mammalian target of rapamycin (mTOR) activator MHY1485 were employed to explore omentin's mechanisms in VNH reduction through HIF-1α inhibition. Omentin treatment reduced VNH in CRF rabbits, concomitant with HIF-1α down-regulation and the suppression of downstream factors, including vascular endothelial growth factor and matrix metalloproteinases. Rh-OMT inhibited TNF-α-induced HVSMC proliferation and migration by modulating both cell cycle and cell adhesion proteins. Additionally, omentin reduced HIF-1α expression through the AMPK/mTOR pathway activation. Notably, the blockade of AMPK/mTOR signaling reversed omentin-mediated inhibition of VNH, cell proliferation, and migration, both in vivo and in vitro. In conclusion, omentin mitigates VNH post-AVF creation by restraining HIF-1α via AMPK/mTOR signaling. Strategies boosting circulating omentin levels may offer promise in averting AVF failure.<br />Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Rabbits
Humans
Cells, Cultured
Male
Kidney Failure, Chronic pathology
TOR Serine-Threonine Kinases metabolism
Graft Occlusion, Vascular pathology
Graft Occlusion, Vascular prevention & control
Graft Occlusion, Vascular metabolism
Graft Occlusion, Vascular physiopathology
Jugular Veins pathology
Jugular Veins metabolism
Jugular Veins transplantation
Hyperplasia
Neointima
Hypoxia-Inducible Factor 1, alpha Subunit metabolism
Hypoxia-Inducible Factor 1, alpha Subunit genetics
Cytokines metabolism
GPI-Linked Proteins metabolism
GPI-Linked Proteins pharmacology
GPI-Linked Proteins genetics
Disease Models, Animal
Cell Proliferation drug effects
Signal Transduction
Myocytes, Smooth Muscle pathology
Myocytes, Smooth Muscle metabolism
Myocytes, Smooth Muscle drug effects
Lectins pharmacology
Lectins metabolism
Cell Movement drug effects
Muscle, Smooth, Vascular pathology
Muscle, Smooth, Vascular metabolism
Muscle, Smooth, Vascular drug effects
AMP-Activated Protein Kinases metabolism
Arteriovenous Shunt, Surgical adverse effects
Subjects
Details
- Language :
- English
- ISSN :
- 1095-9319
- Volume :
- 154
- Database :
- MEDLINE
- Journal :
- Microvascular research
- Publication Type :
- Academic Journal
- Accession number :
- 38640999
- Full Text :
- https://doi.org/10.1016/j.mvr.2024.104688