Inhibition of Tumor Necrosis Factor α–Stimulated Monocyte Adhesion to Human Aortic Endothelial Cells by AMP-Activated Protein Kinase
Abstract
OBJECTIVE: Proatherosclerotic adhesion of leukocytes to the endothelium is attenuated by NO. As AMP-activated protein kinase (AMPK) regulates endothelial NO synthesis, we investigated the modulation of adhesion to cultured human aortic endothelial cells (HAECs) by AMPK. METHODS AND RESULTS: HAECs incubated with the AMPK activator, AICAR, or expressing constitutively active AMPK demonstrated reduced TNFalpha-stimulated adhesion of promonocytic U-937 cells. Rapid inhibition of TNFalpha-stimulated U-937 cell adhesion by AICAR was NO-dependent, associated with unaltered cell surface adhesion molecule expression, and reduced MCP-1 secretion by HAECs. In contrast, inhibition of TNFalpha-stimulated U-937 cell adhesion by prolonged AMPK activation was NO-independent and associated with reduced cell surface adhesion molecule expression. CONCLUSIONS: AMPK activation in HAECs inhibits TNFalpha-stimulated leukocyte adhesion by a rapid NO-dependent mechanism associated with reduced MCP-1 secretion and a late NO-independent mechanism whereby adhesion molecule expression, in particular E-selectin, is suppressed.
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AMPK exerted its anti-inflammatory roles on the vasculature partially via the inhibition of adhesion molecules and chemoattractants by regulating signal transducer and activator of transcription 3, of nuclear factor kappa B, and p300 pathways.
“Indeed, studies have uncovered that AMPK exerted its anti-inflammatory roles on the vasculature partially via the inhibition of adhesion molecules and chemoattractants [248,249,252,253] by regulating signal transducer and activator of transcription 3, of nuclear factor kappa B, and p300 pathways [254,255,256].”
From AMPK, Mitochondrial Function, and Cardiovascular Disease (2020) · cites this paper as [248]
AICAR plays anti-inflammatory roles in vascular cells both in vitro and in vivo.
“Additionally, AICAR, an AMPK activator, plays anti-inflammatory roles in vascular cells both in vitro and in vivo [248,249,250].”
From AMPK, Mitochondrial Function, and Cardiovascular Disease (2020) · cites this paper as [248]
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References 8 · Cited by 57
Research works printed but not linked: 2
- [2]2. Boyle JG, Logan PJ, Ewart MA, Reihill JA, Ritchie SA, Connell JM, Cleland SJ, Salt IP. Rosiglitazone stimulates nitric oxide synthesis in human aortic endothelial cells via AMP-activated protein kinase. J Biol Chem. 2008;283:11210-11217.
- [3]3. Reihill JR, Ewart MA, Hardie DG, Salt IP. AMP-activated protein kinase mediates VEGF-stimulated endothelial NO production. Biochem Biophys Res Commun . 2007;354:1084-1088.
- Authors
- Ewart, M.-A., Kohlhaas, C. F., & Salt, I. P.
- Affiliations
- University of Glasgow (GB)
- Venue
- Arteriosclerosis Thrombosis and Vascular Biology
- Published
- 2008-12
- Volume
- 28
- Issue
- 12
- Pages
- 2255-2257
- ISSN
- 1079-5642 (ISSN-L)
- 1524-4636
- OpenAlex
- W2109565429
- Cited by
- 57
- References
- 8
- Citations by year
- 2024: 1 · 2022: 1 · 2021: 3 · 2020: 3 · 2019: 1 · 2018: 3 · 2017: 2 · 2016: 3 · 2015: 5 · 2014: 3 · 2013: 5 · 2012: 11
- FWCI
- 3.26
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion)
- Funders
- Wellcome Trust
- British Heart Foundation (04/051/17026)
- Topics
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Keywords
- AMPK, TNF-α, monocyte adhesion, endothelial cells, aortic endothelium, nitric oxide, leukocyte adhesion, MCP-1, E-selectin, adhesion molecules, AICAR, atherosclerosis, U937 cells
- MeSH terms
- Aminoimidazole Carboxamide, Cell Adhesion, Cells, Cultured, Enzyme Activation, Enzyme Inhibitors, Humans, Monocytes, Nitric Oxide, Ribonucleotides, Tumor Necrosis Factor-alpha, Intercellular Adhesion Molecule-1, Vascular Cell Adhesion Molecule-1, E-Selectin, NG-Nitroarginine Methyl Ester, U937 Cells, Endothelial Cells, Nitric Oxide Synthase Type III, AMP-Activated Protein Kinases
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