title: Omega-3 polyunsaturated fatty acids reduce vascular endothelial growth factor production and suppress endothelial wound repair.
abstract: Long-chain polyunsaturated omega-3 fatty acids (n-3 PUFAs) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have diverse beneficial effects on cardiovascular diseases and have been used widely as supplements in reducing the risk of cardiovascular diseases. The beneficial effects are believed to be related to the anti-inflammatory and antioxidant action of n-3 PUFA. EPA and DHA can inhibit inflammatory cytokine-induced endothelial activation and reduce endothelial migration and proliferation. Revascularisation is the major therapeutic approach for end-stage cardiovascular diseases, and endothelial migration and proliferation are essential for the success of revascularisation. The aim of this study was to investigate the role of n-3 PUFAs on vascular endothelial wound repair. A scratch-wound repair assay was carried out in cultured human microvascular endothelial cells (HMEC-1) with and without different concentrations of DHA or EPA. The effect of DHA and EPA on HMEC-1 proliferation was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The effect of DHA and EPA on vegf mRNA expression was detected by real-time RT-PCR and vascular endothelial growth factor (VEGF) protein secretion by enzyme-linked immunosorbent assay. DHA and EPA dose-dependently suppressed HMEC-1 cell proliferation and wound repair. DHA and EPA treatment did not induce significant HMEC-1 cell death. The treatment, however, significantly suppressed vegf mRNA expression and protein secretion in both normoxia and hypoxia culture conditions. The addition of exogenous VEGF prevented DHA- and EPA-mediated suppression of HMEC-1 cell proliferation. DHA and EPA have anti-angiogenic effect partially through vegf suppression. The use of DHA and EPA may benefit angiogenic diseases, but may have potential side effects to patients undergoing revascularisation therapy. Further studies will be required to confirm the effect of n-3 PUFAs on vascular repair.
authors.affiliation: Department of Cardiovascular & Thoracic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China. zhuangweihy@sina.com
authors.forename: Wei
authors.initials: W
authors.lastname: Zhuang
authors.forename: Guo
authors.initials: G
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Lin
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Deng
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015687:Cell Hypoxia; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D020533:Angiogenesis Inhibitors; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid