Expression of bioactive lysophospholipids and processing enzymes in the vitreous from patients with proliferative diabetic retinopathy

Lipids in Health and Disease

Research

Ahmed Mousa¹  Mohammad Mairaj Siddiquei¹  Kaiser Alam¹  Mohd Imtiaz Nawaz¹  Ghulam Mohammad¹  Ahmed M Abu El-Asrar²  Ghislain Opdenakker³ 

[1] Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia;Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia;Dr. Nasser Al-Rashid Research Chair in Ophthalmology, King Saud University, Riyadh, Saudi Arabia;Rega Institute for Medical Research, Department of Microbiology and Immunology, University of Leuven, Leuven, KU, Belgium;

关键词: Proliferative diabetic retinopathy;    Lysophospholipids;    Phosphatidic acid;    Lysophosphatidic acid;    Sphingosine-1-phosphate lyase;    Phospholipase A1;   

DOI  :  10.1186/1476-511X-13-187

 received in 2014-06-19, accepted in 2014-12-04,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundThe 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).MethodsVitreous samples from 34 PDR and 29 nondiabetic patients were studied by biochemical and enzyme-linked immunosorbent assays and Western blot analysis.ResultsPA, 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.ConclusionsOur 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.

【 授权许可】

CC BY   
© Abu El-Asrar et al.; licensee BioMed Central. 2014