title: Fish oil-enriched diet protects against ischemia by improving angiogenesis, endothelial progenitor cell function and postnatal neovascularization.
abstract: BACKGROUND
  Fish oil consumption has been associated with a reduced incidence of cardiovascular diseases. However, the precise mechanisms involved are not completely understood. Here we tested the hypothesis that a fish oil-enriched diet improves neovascularization in response to ischemia.
  
  
  RESULTS
  C57Bl/6 mice were fed a diet containing either 20% fish oil, rich in long-chain n-3 polyunsaturated fatty acids (PUFAs), or 20% corn oil, rich in n-6 PUFAs. After 4 weeks, hindlimb ischemia was surgically induced by femoral artery removal. We found that blood flow recovery was significantly improved in mice fed a fish oil diet compared to those fed a corn oil diet (Doppler flow ratio (DFR) at day 21 after surgery 78 ± 5 vs. 56 ± 4; p < 0.01). Clinically, this was associated with a significant reduction of ambulatory impairment and ischemic damage in the fish oil group. At the microvascular level, capillary density was significantly improved in ischemic muscles of mice fed a fish oil diet. This correlated with increased expression of VEGF and eNOS in ischemic muscles, and higher NO concentration in the plasma. Endothelial progenitor cells (EPCs) have been shown to have an important role for postnatal neovascularization. We found that the number of EPCs was significantly increased in mice fed a fish oil diet. In addition, oxidative stress levels (DCF-DA, DHE) were reduced in EPCs isolated from mice exposed to fish oil, and this was associated with improved EPC functional activities (migration and integration into tubules). In vitro, treatment of EPCs with fish oil resulted in a significant increase of cellular migration. In addition, the secretion of angiogenic growth factors including IL6 and leptin was significantly increased in EPCs exposed to fish oil.
  
  
  CONCLUSIONS
  Fish oil-enriched diet is associated with improved neovascularization in response to ischemia. Potential mechanisms involved include activation of VEGF/NO pathway in ischemic tissues together with an increase in the number and the functional activities of EPCs.
authors.affiliation: Department of Cardiovascular Research, Centre Hospitalier de l'Université de Montréal, 1560 Sherbrooke Est, Montréal, Québec H2L 4M1, Canada.
authors.forename: Julie
authors.initials: J
authors.lastname: Turgeon
authors.forename: Sylvie
authors.initials: S
authors.lastname: Dussault
authors.forename: Fritz
authors.initials: F
authors.lastname: Maingrette
authors.forename: Jessika
authors.initials: J
authors.lastname: Groleau
authors.forename: Paola
authors.initials: P
authors.lastname: Haddad
authors.forename: Gemma
authors.initials: G
authors.lastname: Perez
authors.forename: Alain
authors.initials: A
authors.lastname: Rivard
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D000818:Animals; D001835:Body Weight; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D003314:Corn Oil / Q000494:pharmacology; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D005260:Female; D005395:Fish Oils / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D006614:Hindlimb / Q000098:blood supply; D007511:Ischemia / Q000178:diet therapy / Q000503:physiopathology / Q000517:prevention & control*; D008055:Lipids / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D043925:Angiogenesis Inducing Agents; D005395:Fish Oils; D008055:Lipids; D003314:Corn Oil
keywords: Angiogenesis; Endothelial progenitor cells; Fish oil; Neovascularization; Omega-3 fatty acids