title: Docosahexaenoic acid monoacylglyceride decreases endothelin-1 induced Ca(2+) sensitivity and proliferation in human pulmonary arteries.
abstract: BACKGROUND
  Pulmonary artery vasoconstriction and vascular remodeling contribute to a sustained elevation of pulmonary vascular resistance and pressure in patients with pulmonary arterial hypertension (PH), an often fatal hemodynamic disease. The effect of docosahexaenoic acid monoacylglyceride (MAG-DHA) and the role of the 17 kDa protein kinase C-potentiated inhibitor protein (CPI-17) were determined on vasoconstriction and smooth muscle cell proliferation of human pulmonary arteries (HPA).
  
  
  METHODS
  HPA were obtained from 16 patients undergoing lung resection for carcinoma. The mechanical tension and Ca(2+) sensitivity were measured on arterial rings treated with endothelin-1 (ET-1) in the absence or presence of MAG-DHA. The effect of MAG-DHA on the level of proliferation of smooth muscle cells isolated from HPA was evaluated in order to determine the role of CPI-17 protein.
  
  
  RESULTS
  MAG-DHA treatment decreased the reactivity and Ca(2+) sensitivity induced by ET-1 in HPA. MAG-DHA treatment also decreased the expression of vascular endothelial growth factor (VEGF) induced by ET-1. Moreover, both VEGF inhibitor and MAG-DHA treatments reduced Ca(2+) hypersensitivity induced by ET-1, which was associated to a reduction in CPI-17 and myosin-binding subunit of the myosin light chain phosphatase (MYPT-1) phosphorylation levels. Proliferation of ET-1-stimulated HPA smooth muscle cells (PASMc) was also decreased following CPI-17 small interfering RNA transfection and MAG-DHA treatments. Western blot analyses revealed that MAG-DHA treatment resulted in decreased phosphorylation levels of CPI-17 and extracellular signal-regulated kinases (ERK) in PASMc treated with ET-1.
  
  
  CONCLUSIONS
  We have demonstrated that VEGF interacts with CPI-17 signaling pathway resulting in an increase in Ca(2+) sensitivity and proliferation of PASMc, whereas MAG-DHA treatment reversed these effects.
authors.affiliation: SCF Pharma, Ste-Luce, Quebec, Canada.
authors.forename: Caroline
authors.initials: C
authors.lastname: Morin
authors.forename: Samuel
authors.initials: S
authors.lastname: Fortin
authors.forename: Eric
authors.initials: E
authors.lastname: Rousseau
mesh_terms: D002118:Calcium / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D019332:Endothelin-1 / Q000494:pharmacology*; D006801:Humans; D006976:Hypertension, Pulmonary; D047908:Intracellular Signaling Peptides and Proteins; D050178:Monoglycerides / Q000494:pharmacology*; D009124:Muscle Proteins; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D011651:Pulmonary Artery / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D019332:Endothelin-1; D047908:Intracellular Signaling Peptides and Proteins; D050178:Monoglycerides; D009124:Muscle Proteins; C107507:PPP1R14A protein, human; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C575982:docosahexaenoic acid monoacylglyceride; D010749:Phosphoprotein Phosphatases; D002118:Calcium