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Cited by 105Fatty Acid Research and HealthAtherosclerosis and Cardiovascular DiseasesLipoproteins and Cardiovascular Health

Resolvin E1 attenuates atherosclerosis in absence of cholesterol-lowering effects and on top of atorvastatin

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Salic, Kanita, Morrison, Martine C., Verschuren, Lars, Wielinga, Peter Y., Wu, Lijun, Kleemann, Robert, Gjorstrup, Per, Kooistra, Teake·2016·Atherosclerosis
DOI 10.1016/j.atherosclerosis.2016.05.001
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Abstract

BACKGROUND AND AIMS: Besides LDL-cholesterol, local vascular inflammation plays a key role in atherogenesis. Efficient therapies to treat the inflammatory component of the disease have not been established. The discovery of specialized inflammation-resolving mediators, such as resolvins may provide new opportunities for treatment. This study examines whether the ω-3 fatty acid eicosapentaenoic acid-derived resolvin E1 (RvE1), can reduce atherosclerosis, when administered alone or in combination with a cholesterol-lowering statin. METHODS: ApoE*3Leiden mice were fed a hypercholesterolemic diet for 9 weeks and subsequently treated with RvE1-low (1 mg/kg/day), RvE1-high (5 mg/kg/day), atorvastatin (1.5 mg/kg/day) or the combination of atorvastatin and RvE1-low for the following 16 weeks. RESULTS: RvE1-low and RvE1-high reduced atherosclerotic lesion size to the same extent (-35%; p < 0.05), attenuated the formation of severe lesions, also seen as a proportional increase in the presence of mild lesions, but did not alter plasma cholesterol levels. Cholesterol-lowering atorvastatin reduced atherosclerosis (-27%, p < 0.05), and the combination of RvE1 and atorvastatin further attenuated lesion size (-51%, p < 0.01) and increased the content of mild lesions. RvE1 did not affect plasma SAA, E-selectin, VCAM-1 or MCP-1 but did reduce plasma EPHX4 and down-regulated the local expression of pro-atherogenic genes in the aortae, (e.g. Cd74, Cd44, Ccl2, Ccr5 and Adam17) and significantly inactivated IFN-γ (p < 0.001) and TNF-α (p < 0.001) signalling pathways. CONCLUSIONS: RvE1 attenuates atherogenesis both alone and on top of a statin. The local effects of RvE1 are demonstrated by the modulated aortic expression of genes involved in inflammatory and immune responses, without altering plasma cholesterol or circulating SAA.

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Authors
Salic, K., Morrison, M. C., Verschuren, L., Wielinga, P. Y., Wu, L., Kleemann, R., Gjorstrup, P., & Kooistra, T.
Affiliations
Netherlands Organisation for Applied Scientific Research (NL)
Corresponding author
  • Salic, Kanita
  • Gjorstrup, Per
ORCID
Venue
Atherosclerosis
Publisher
Elsevier BV
Published
2016-07
Volume
250
Pages
158-165
ISSN
0021-9150 (ISSN-L)
DOI
10.1016/j.atherosclerosis.2016.05.001
OpenAlex
W2347152603
Cited by
105
References
42
Citations by year
2026: 6 · 2025: 4 · 2024: 7 · 2023: 9 · 2022: 20 · 2021: 10 · 2020: 8 · 2019: 12 · 2018: 12 · 2017: 13 · 2016: 4
FWCI
14.27
Type
journal article
Language
en
Open access
Licence
Locations
  • Atherosclerosis (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
  • Leiden Repository (Leiden University) (submittedVersion)
  • TNO Repository (submittedVersion)
  • Repository hosted by TU Delft Library (TU Delft) (submittedVersion)
Topics
  • Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
  • Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
Keywords
resolvin E1, atorvastatin, eicosapentaenoic acid, omega-3 fatty acids, vascular inflammation, hypercholesterolemia, atherosclerotic plaque, TNF-alpha signalling, aortic gene expression, statin combination therapy
MeSH terms
Atorvastatin, Mice, Knockout, ApoE, Serum Amyloid A Protein, Animals, Aorta, Cholesterol, Female, Inflammation, Lipids, Cholesterol, LDL, Eicosapentaenoic Acid, Fatty Acids, Omega-3, Treatment Outcome, Vascular Cell Adhesion Molecule-1, E-Selectin, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Oligonucleotide Array Sequence Analysis, Atherosclerosis, Mice

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