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

Lipids in Health and Disease

Ghislain Opdenakker²  Ahmed Mousa³  Kaiser Alam³  Mohammad Mairaj Siddiquei³  Ghulam Mohammad³  Mohd Imtiaz Nawaz³  Ahmed M Abu El-Asrar¹ 

[1] 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;Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia

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

Others  :  1151649
DOI  :  10.1186/1476-511X-13-187

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

【 摘 要 】

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.

【 授权许可】

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

【 图 表 】

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