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: Caroline Morin, Roddy Hiram, Eric Rousseau, Pierre U Blier, Samuel Fortin
• Journal: American journal of physiology. Heart and circulatory physiology (Am J Physiol Heart Circ Physiol) Vol. 307 Issue 4 Pg. H574-86 (Aug 15 2014) ISSN: 1522-1539 [Electronic] United States
• PMID: 24929859 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 1-O-docosapentaenoylglycerol
• Fatty Acids, Unsaturated
• Monoglycerides
• NF-kappa B
• Vascular Endothelial Growth Factor A
• Arachidonic Acid
• p38 Mitogen-Activated Protein Kinases
• Matrix Metalloproteinase 2
• Mmp2 protein, rat
• Matrix Metalloproteinase 9
• Mmp9 protein, rat
• docosapentaenoic acid

Topics

• Animals
• Arachidonic Acid (metabolism)
• Arterioles (drug effects, pathology)
• Fatty Acids, Unsaturated (pharmacology, therapeutic use)
• Hypertension, Pulmonary (drug therapy)
• Inflammation (drug therapy)
• Lipid Metabolism
• Lung (blood supply, metabolism)
• Male
• Matrix Metalloproteinase 2 (genetics, metabolism)
• Matrix Metalloproteinase 9 (genetics, metabolism)
• Monoglycerides (pharmacology, therapeutic use)
• NF-kappa B (metabolism)
• Rats
• Rats, Wistar
• Vascular Endothelial Growth Factor A (genetics, metabolism)
• Vascular Remodeling (drug effects)
• p38 Mitogen-Activated Protein Kinases (metabolism)