Aspirin-Triggered Lipoxin and Resolvin E1 Modulate Vascular Smooth Muscle Phenotype and Correlate with Peripheral Atherosclerosis
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Atherosclerosis is a chronic inflammatory disease of the vessel wall. Recent evidence suggests that chronic vascular inflammation ensues as an imbalance between pro- and anti-inflammatory mediators. Recently identified lipid mediators (eg, lipoxins and resolvins) play active roles in promoting the resolution of inflammation. Alterations in vascular smooth muscle cell (VSMC) phenotype, which manifest as a loss of contractile protein expression and increased proliferation and migration, are prominent mechanistic features of both atherosclerosis and restenosis following various interventions (eg, angioplasty and bypass grafting). We sought to determine whether human atherosclerosis is associated with a "resolution deficit" and whether lipoxins and resolvins influence VSMC phenotype. Here we report that plasma levels of aspirin-triggered lipoxin are significantly lower in patients with symptomatic peripheral artery disease than in healthy volunteers. Both aspirin-triggered lipoxin and resolvin E1 block platelet-derived growth factor-stimulated migration of human saphenous vein SMCs and decrease phosphorylation of the platelet-derived growth factor receptor-β. Importantly, receptors for aspirin-triggered lipoxin and resolvin E1 (ALX and ChemR23, respectively) were identified in human VSMCs. Overall, these results demonstrate that stimulatory lipid mediators confer a protective phenotypic switch in VSMCs and elucidate new functions for these mediators in the regulation of SMC biology. These results also suggest that peripheral artery disease is associated with an inflammation-resolution deficit and highlight a potential therapeutic opportunity for the regulation of vascular injury responses.
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Lesional macrophages are the principal target of Ac2-26 in these studies, although SPMs might also interact with lesional smooth muscle cells and endothelial cells.
“Although the above data suggest that lesional macrophages are the principal target of Ac2–26 in these studies, SPMs might also interact with lesional smooth muscle cells and endothelial cells107,110.”
From Inflammation and its resolution in atherosclerosis: mediators and therapeutic opportunities (2019) · cites this paper as [107]
Plasma levels of LXA4 are decreased in patients with peripheral artery disease compared with healthy controls.
“Plasma levels of another 5-LOX-derived SPM, LXA4, are decreased in patients with peripheral artery disease compared with healthy controls107.”
From Inflammation and its resolution in atherosclerosis: mediators and therapeutic opportunities (2019) · cites this paper as [107]
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- Authors
- Ho, K. J., Spite, M., Owens, C. D., Lancero, H., Kroemer, A. H. K., Pande, R., Creager, M. A., Serhan, C. N., & Conte, M. S.
- Affiliations
- Brigham and Women's Hospital (US)
- University of California, San Francisco (US)
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Conte, Michael S.
- ORCID
- Venue
- The American Journal of Pathology
- Publisher
- Elsevier BV
- Published
- 2010-10
- Volume
- 177
- Issue
- 4
- Pages
- 2116-2123
- ISSN
- 0002-9440 (ISSN-L)
- PMC
- PMC2947304
- OpenAlex
- W2003076495
- Cited by
- 204
- References
- 31
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 14 · 2023: 13 · 2022: 17 · 2021: 14 · 2020: 10 · 2019: 16 · 2018: 18 · 2017: 15 · 2016: 16 · 2015: 15 · 2014: 13 · 2013: 14 · 2012: 10
- FWCI
- 10.62
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- American Journal Of Pathology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (HL087526, HL75771, K23 HL-92163, P20-RR024489, P50-DE016191)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
- Keywords
- aspirin-triggered lipoxins, resolvin E1, vascular smooth muscle cells, peripheral arterial disease, atherosclerosis, inflammation resolution, PDGFRβ, ChemR23, smooth muscle cell migration, vascular inflammation, lipid mediators
- MeSH terms
- Aged, Anti-Inflammatory Agents, Aspirin, Cell Survival, Chemotaxis, Female, Flow Cytometry, Humans, Immunoenzyme Techniques, Male, Middle Aged, Muscle, Smooth, Vascular, Phenotype, Phosphorylation, Platelet-Derived Growth Factor, Prospective Studies, RNA, Messenger, Saphenous Vein, Eicosapentaenoic Acid, Blotting, Western, Case-Control Studies, Receptors, Platelet-Derived Growth Factor, Receptors, Chemokine, Reverse Transcriptase Polymerase Chain Reaction, Lipoxins, Adaptor Proteins, Signal Transducing, Atherosclerosis, Peripheral Arterial Disease
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