Resolvin E1 (RvE1) Attenuates Atherosclerotic Plaque Formation in Diet and Inflammation-Induced Atherogenesis
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Objective—: Epidemiological and recent clinical studies implicate periodontitis as an independent risk factor for cardiovascular disease. Previously, we demonstrated that rabbits with experimental periodontitis and cholesterol diet exhibit more aortic plaque compared with diet alone. We also showed that a proresolution mediator, Resolvin E1 (RvE1), reverses the experimental periodontitis. Here, we determined whether oral/topical application of RvE1 attenuates aortic atherosclerosis induced by both diet and periodontal inflammation. Approach and Results—: Thirty-nine rabbits on a 13-week regimen of 0.5% cholesterol diet were included. Periodontitis was induced by Porphyromonas gingivalis in 24 rabbits and 15 rabbits were placed in no-periodontitis groups. Interventions were no-treatment, vehicle, and RvE1 treatment (4 μg/site or 0.4 μg/site) topically applied 3× per week. At 13 weeks, both periodontitis and atherosclerosis were quantified. Atherosclerotic plaques were assessed by Sudan IV staining, histology, and ex vivo MRI. Serum levels of C-reactive protein were evaluated as a measure of systemic inflammation. RvE1, used as an oral/topical agent, significantly diminished atherogenesis and prevented periodontitis ( P <0.05). In the absence of periodontal inflammation, oral/topical application of RvE1 resulted in significantly less arterial plaque, a lower intima/media ratio, and decreased inflammatory cell infiltration compared with no-treatment ( P <0.001). Local oral RvE1 application significantly reduced systemic levels of C-reactive protein ( P <0.05). Conclusions—: The results suggest that oral/topical RvE1 attenuates enhanced atherogenesis induced by periodontitis and prevents vascular inflammation and atherogenesis in the absence of periodontitis. The inhibition of vascular inflammation with endogenous mediators of resolution of inflammation provides a novel approach in the prevention of atherogenic events.
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Exogenous administration of RvE1 reduces experimental atherosclerosis.
“exogenous administration of RvE1 reduces experimental atherosclerosis118,119.”
From Inflammation and its resolution in atherosclerosis: mediators and therapeutic opportunities (2019) · cites this paper as [118]
Treatment of Western-diet-fed Ldlr−/− mice with athero-targeted nanoparticles carrying an annexin A1-derived pro-resolving peptide Ac2-26 or with SPMs markedly suppressed formation of necrotic, thin-capped plaques.
“As summarized in this Review, treatment of Western-diet-fed Ldlr−/− mice with athero-targeted nanoparticles packaged with a pro-resolving peptide derived from annexin A1 (Ac2–26) or with SPMs markedly suppressed the formation of necrotic, thin-capped plaques36,38,99,109,118.”
From Inflammation and its resolution in atherosclerosis: mediators and therapeutic opportunities (2019) · cites this paper as [118]
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References 58 · Cited by 199
- Authors
- Hasturk, H., Abdallah, R., Kantarci, A., Nguyen, D., Giordano, N., Hamilton, J., & Van Dyke, T. E.
- Affiliations
- From the Department of Applied Oral Sciences, Center for Periodontology, The Forsyth Institute, Cambridge, MA (H.H., A.K., D.N., T.E.V.D.); Department of Biological and Diagnostic Sciences, Beirut Arab University, Beirut, Lebanon (R.A.); Department of Biophysics, Boston University School of Medicine, MA (J.H.); and Department of Biomedical Engineering, Boston University, MA (N.G.).
- Boston University (US)
- Venue
- Arteriosclerosis, Thrombosis, and Vascular Biology
- Published
- 2015-05
- Volume
- 35
- Issue
- 5
- Pages
- 1123-1133
- ISSN
- 1079-5642 (ISSN-L)
- 1524-4636
- PMC
- PMC4415167
- OpenAlex
- W2099005050
- Cited by
- 199
- References
- 58
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 15 · 2023: 19 · 2022: 27 · 2021: 25 · 2020: 18 · 2019: 16 · 2018: 15 · 2017: 19 · 2016: 18 · 2015: 11 · 2014: 1
- FWCI
- 28.42
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Brigham and Women's Hospital
- U.S. Public Health Service (DE-15566, DE19938)
- National Institute of Dental and Craniofacial Research (R01DE019938, DE18917, DE 19938, P50DE016191, DE15566, R01DE015566, K23DE018917)
- Topics
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Keywords
- resolvin E1, atherosclerosis, periodontitis, Porphyromonas gingivalis, cholesterol diet, vascular inflammation, inflammation resolution, aortic plaque, C-reactive protein, topical application, oral administration, rabbits
- MeSH terms
- Administration, Topical, Animals, Biopsy, Needle, C-Reactive Protein, Diet, Atherogenic, Disease Models, Animal, Immunohistochemistry, Inflammation, Male, Periodontitis, Rabbits, Random Allocation, Reference Values, Eicosapentaenoic Acid, Treatment Outcome, Risk Assessment, Atherosclerosis
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