title: Docosapentaenoic acid monoacylglyceride reduces inflammation and vascular remodeling in experimental pulmonary hypertension.
abstract: n-3 Polyunsaturated fatty acids (n-3 PUFA) have been shown to reduce inflammation and proliferation of pulmonary artery smooth muscle cells under pathophysiological conditions. However, the anti-inflammatory effect of the newly synthesized docosapentaenoic acid monoacylglyceride (MAG-DPA) on key signaling pathways in pulmonary hypertension (PH) pathogenesis has yet to be assessed. The aim of the present study was to determine the effects of MAG-DPA on pulmonary inflammation and remodeling occurring in a rat model of PH, induced by a single injection of monocrotaline (MCT: 60 mg/kg). Our results demonstrate that MAG-DPA treatment for 3 wk following MCT injection resulted in a significant improvement of right ventricular hypertrophy (RVH) and a reduction in Fulton's Index (FI). Morphometric analyses revealed that the wall thickness of pulmonary arterioles was significantly lower in MCT + MAG-DPA-treated rats compared with controls. This result was further correlated with a decrease in Ki-67 immunostaining. Following MAG-DPA treatments, lipid analysis showed a consistent increase in DPA together with lower levels of arachidonic acid (AA), as measured in blood and tissue samples. Furthermore, in MCT-treated rats, oral administration of MAG-DPA decreased NF-κB and p38 MAPK activation, leading to a reduction in MMP-2, MMP-9, and VEGF expression levels in lung tissue homogenates. Altogether, these data provide new evidence regarding the mode of action of MAG-DPA in the prevention of pulmonary hypertension induced by MCT.
authors.forename: Caroline
authors.initials: C
authors.lastname: Morin
authors.forename: Roddy
authors.initials: R
authors.lastname: Hiram
authors.forename: Eric
authors.initials: E
authors.lastname: Rousseau
authors.forename: Pierre U
authors.initials: PU
authors.lastname: Blier
authors.forename: Samuel
authors.initials: S
authors.lastname: Fortin
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001160:Arterioles / Q000187:drug effects* / Q000473:pathology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology / Q000627:therapeutic use*; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D007249:Inflammation / Q000188:drug therapy; D050356:Lipid Metabolism; D008168:Lung / Q000098:blood supply / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D050178:Monoglycerides / Q000494:pharmacology / Q000627:therapeutic use*; D016328:NF-kappa B / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D066253:Vascular Remodeling / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C000596377:1-O-docosapentaenoylglycerol; D005231:Fatty Acids, Unsaturated; D050178:Monoglycerides; D016328:NF-kappa B; D042461:Vascular Endothelial Growth Factor A; D016718:Arachidonic Acid; D048051:p38 Mitogen-Activated Protein Kinases; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat; C026219:docosapentaenoic acid