title: Expression of bioactive lysophospholipids and processing enzymes in the vitreous from patients with proliferative diabetic retinopathy.
abstract: BACKGROUND
  The bioactive lysophospholipids phosphatidic acid (PA), lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) have been implicated in mediating cell migration, proliferation and apoptosis, inflammation, angiogenesis and fibrosis. This study was conducted to measure the levels of PA, LPA, LPA-producing enzymes phospholipase A1/A2 (PLA1A/PLA2, respectively) and acylgylycerol kinase (AGK), the S1P receptor S1PR1, the S1P catabolising enzyme S1P lyase (SPL) and 5-lipoxygenase in the vitreous fluid from patients with proliferative diabetic retinopathy (PDR). In addition, we investigated the correlations between the levels of PA and LPA and the levels of the inflammatory and endothelial dysfunction biomarker soluble vascular cell adhesion molecule-1 (sVCAM-1).
  
  
  METHODS
  Vitreous samples from 34 PDR and 29 nondiabetic patients were studied by biochemical and enzyme-linked immunosorbent assays and Western blot analysis.
  
  
  RESULTS
  PA, LPA and sVCAM-1 levels in vitreous samples from PDR patients were significantly higher than those in nondiabetic patients. Significant correlations were observed between levels of LPA and levels of PA and sVCAM-1. Western blot analysis revealed a significant increase in the expression of PLA1A, AGK, S1PR1 and SPL in vitreous samples from PDR patients compared to nondiabetic controls, whereas PLA2 and 5-lipoxygenase were not detected.
  
  
  CONCLUSIONS
  Our findings suggest that the enzymatic activities of PLA1A and AGK might be responsible for increased synthesis of LPA in PDR and that PLA1A, but not PLA2 is responsible for deacylation of PA to generate LPA. S1PR1 and SPL might regulate inflammatory, angiogenic and fibrogenic responses in PDR.
authors.affiliation: Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia. abuasrar@ksu.edu.sa.
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Abu El-Asrar
authors.forename: Mohd Imtiaz
authors.initials: MI
authors.lastname: Nawaz
authors.forename: Ghulam
authors.initials: G
authors.lastname: Mohammad
authors.forename: Mohammad Mairaj
authors.initials: MM
authors.lastname: Siddiquei
authors.forename: Kaiser
authors.initials: K
authors.lastname: Alam
authors.forename: Ahmed
authors.initials: A
authors.lastname: Mousa
authors.forename: Ghislain
authors.initials: G
authors.lastname: Opdenakker
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D003930:Diabetic Retinopathy / Q000201:enzymology*; D005260:Female; D006801:Humans; D008246:Lysophospholipids / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D054466:Phospholipases A1 / Q000378:metabolism*; D054467:Phospholipases A2 / Q000378:metabolism*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D049349:Receptors, Lysosphingolipid / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives / Q000378:metabolism; D000081025:Sphingosine-1-Phosphate Receptors; D014822:Vitreous Body / Q000201:enzymology
chemical_list: D008246:Lysophospholipids; D049349:Receptors, Lysosphingolipid; C477362:S1PR1 protein, human; D000081025:Sphingosine-1-Phosphate Receptors; C060506:sphingosine 1-phosphate; C492429:AGK protein, human; D017853:Phosphotransferases (Alcohol Group Acceptor); C512665:PLA1A protein, human; D054466:Phospholipases A1; D054467:Phospholipases A2; D013110:Sphingosine; C032881:lysophosphatidic acid