title: Aspirin enhances protective effect of fish oil against thrombosis and injury-induced vascular remodelling.
abstract: OBJECTIVE
  Although aspirin (acetylsalicylic acid) is commonly used to prevent ischaemic events in patients with coronary artery disease, many patients fail to respond to aspirin treatment. Dietary fish oil (FO), containing ω3 polyunsaturated fatty acids (PUFAs), has anti-inflammatory and cardio-protective properties, such as lowering cholesterol and modulating platelet activity. The objective of the present study was to investigate the potential additional effects of aspirin and FO on platelet activity and vascular response to injury.
  
  
  METHODS
  Femoral arterial remodelling was induced by wire injury in mice. Platelet aggregation, and photochemical- and ferric chloride-induced carotid artery thrombosis were employed to evaluate platelet function.
  
  
  RESULTS
  FO treatment increased membrane ω3 PUFA incorporation, lowered plasma triglyceride and cholesterol levels, and reduced systolic BP in mice. FO or aspirin alone inhibited platelet aggregation; however, when combined, they exhibited synergistic suppression of platelet activity in mice, independent of COX-1 inhibition. FO alone, but not aspirin, attenuated arterial neointimal growth in response to injury. Strikingly, a combination of FO and aspirin synergistically inhibited injury-induced neointimal hyperplasia and reduced perivascular inflammatory reactions. Moreover, co-administration of FO and aspirin decreased the expression of pro-inflammatory cytokines and adhesion molecules in inflammatory cells. Consistently, a pro-resolution lipid mediator-Resolvin E1, was significantly elevated in plasma in FO/aspirin-treated mice.
  
  
  CONCLUSIONS
  Co-administration of FO and low-dose aspirin may act synergistically to protect against thrombosis and injury-induced vascular remodelling in mice. Our results support further investigation of adjuvant FO supplementation for patients with stable coronary artery disease.
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Shanghai, China.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Gong
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Shanghai, China.
authors.forename: Minghui
authors.initials: M
authors.lastname: Lin
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Shanghai, China.
authors.forename: Lingjuan
authors.initials: L
authors.lastname: Piao
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada.
authors.forename: Xinzhi
authors.initials: X
authors.lastname: Li
authors.affiliation: Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, MOH Key Lab of Thrombosis and Hemostasis, Jiangsu Institute of Hematology, The First Affiliated Hospital, Soochow University, Suzhou, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Yang
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Shanghai, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Shanghai, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Xiao
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Shanghai, China.
authors.forename: Qingli
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Bridgeport Hospital, Yale New Haven Health System, Bridgeport, CT, USA.
authors.forename: Wen-Liang
authors.initials: WL
authors.lastname: Song
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Shanghai, China.
authors.forename: Huiyong
authors.initials: H
authors.lastname: Yin
authors.affiliation: Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, MOH Key Lab of Thrombosis and Hemostasis, Jiangsu Institute of Hematology, The First Affiliated Hospital, Soochow University, Suzhou, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada.
authors.forename: Colin D
authors.initials: CD
authors.lastname: Funk
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Shanghai, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yu
mesh_terms: D000818:Animals; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology*; D002712:Chlorides; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005263:Femoral Artery / Q000187:drug effects* / Q000473:pathology; D005290:Ferric Compounds; D005395:Fish Oils / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D055668:Photochemical Processes; D010974:Platelet Aggregation / Q000187:drug effects; D013329:Structure-Activity Relationship; D013927:Thrombosis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D057772:Vascular System Injuries / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*
chemical_list: D002712:Chlorides; D005290:Ferric Compounds; D005395:Fish Oils; D001241:Aspirin; C024555:ferric chloride