title: Lysophosphatidic acid causes endothelial dysfunction in porcine coronary arteries and human coronary artery endothelial cells.
abstract: OBJECTIVE
  The objective of this study was to determine the effects of lysophosphatidic acid (LPA) on endothelial functions and molecular alternations in both porcine coronary arteries and human coronary artery endothelial cells (HCAECs).
  
  
  RESULTS
  The vessel rings and HCAECs were treated with clinically relevant concentrations of LPA for different times. Vasomotor reactivity was studied with a myograph tension system. LPA (10 and 50 μM) treatment for the vessel rings significantly reduced endothelium-dependent vasorelaxation in response to bradykinin (×10(-5)M) by 32% and 49%, respectively, compared with the control (P<0.05). LPA decreased endothelial nitric oxide synthase (eNOS) mRNA and immunoreactivity levels in the vessel rings. In HCAECs, LPA reduced eNOS mRNA, phospho-eNOS and total eNOS protein levels. In addition, superoxide anion levels in LPA-treated vessel rings and HCAECs were significantly increased by lucegenin-enhanced chemiluminescence assay and dihydroethidium staining, respectively. Mitochondrial membrane potential and ATP content in LPA-treated HCAECs were substantially decreased. The mRNA levels of reactive oxygen species generating enzymes NOX4 and p40(phox) were increased, while endogenous antioxidant enzyme superoxide dismutase 1 was decreased in response to LPA treatment in HCAECs. Furthermore, exogenous antioxidant molecule selenomethionine (SeMet) effectively reversed these LPA-induced effects in both porcine coronary arteries and HCAECs.
  
  
  CONCLUSIONS
  LPA causes endothelial dysfunction by a mechanism associated with decreased eNOS expression and increased oxidative stress in porcine coronary arteries and HCAECs.
authors.affiliation: Molecular Surgeon Research Center, Division of Vascular Surgery and Endovascular Therapy, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA. jchen@bcm.tmc.edu
authors.forename: Chanygi
authors.initials: C
authors.lastname: Chen
authors.forename: Lyssa N
authors.initials: LN
authors.lastname: Ochoa
authors.forename: Anna
authors.initials: A
authors.lastname: Kagan
authors.forename: Hong
authors.initials: H
authors.lastname: Chai
authors.forename: Zhengdong
authors.initials: Z
authors.lastname: Liang
authors.forename: Peter H
authors.initials: PH
authors.lastname: Lin
authors.forename: Qizhi
authors.initials: Q
authors.lastname: Yao
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000503:physiopathology*; D001920:Bradykinin / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects*; D015536:Down-Regulation; D004730:Endothelium, Vascular / Q000187:drug effects; D006801:Humans; D008246:Lysophospholipids / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis; D018384:Oxidative Stress / Q000187:drug effects; D012645:Selenomethionine / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D013481:Superoxides / Q000378:metabolism; D013552:Swine; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D008246:Lysophospholipids; C000606290:SOD1 protein, human; D013481:Superoxides; D012645:Selenomethionine; D052250:Nitric Oxide Synthase Type III; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; C032881:lysophosphatidic acid; D001920:Bradykinin