title: Resolvin E1 (RvE1) Attenuates Atherosclerotic Plaque Formation in Diet and Inflammation-Induced Atherogenesis.
abstract: 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.
  
  
  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.
authors: 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.). hhasturk@forsyth.org tvandyke@forsyth.org.
authors: Hatice
authors: H
authors: Hasturk
authors: 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.).
authors: Rima
authors: R
authors: Abdallah
authors: 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.).
authors: Alpdogan
authors: A
authors: Kantarci
authors: 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.).
authors: Daniel
authors: D
authors: Nguyen
authors: 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.).
authors: Nicholas
authors: N
authors: Giordano
authors: 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.).
authors: James
authors: J
authors: Hamilton
authors: 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.). hhasturk@forsyth.org tvandyke@forsyth.org.
authors: Thomas E
authors: TE
authors: Van Dyke
mesh_terms: D000287:Administration, Topical; D000818:Animals; D050197:Atherosclerosis / Q000473:pathology* / Q000517:prevention & control; D001707:Biopsy, Needle; D002097:C-Reactive Protein / Q000378:metabolism; D004036:Diet, Atherogenic; D004195:Disease Models, Animal; D015118:Eicosapentaenoic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D007150:Immunohistochemistry; D007249:Inflammation / Q000150:complications / Q000503:physiopathology; D008297:Male; D010518:Periodontitis / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D011817:Rabbits; D011897:Random Allocation; D012016:Reference Values; D018570:Risk Assessment; D016896:Treatment Outcome
chemical_list: D002097:C-Reactive Protein; D015118:Eicosapentaenoic Acid; C499823:5S,12R,18R-trihydroxy-6Z,8E,10E,14Z,16E-eicosapentaenoic acid
keywords: atherosclerosis; inflammation; models, animal