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. 2014 Dec 11:13:187.
doi: 10.1186/1476-511X-13-187.

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

Ahmed M Abu El-Asrar  1 , Mohd Imtiaz Nawaz, Ghulam Mohammad, Mohammad Mairaj Siddiquei, Kaiser Alam, Ahmed Mousa, Ghislain Opdenakker
Affiliations

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

Ahmed M Abu El-Asrar et al. Lipids Health Dis. .

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.

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Figures

Figure 1
Figure 1
Comparisons of mean phosphatidic acid (PA), lysophosphatidic acid (LPA) and soluble vascular cell adhesion molecule-1 (sVCAM-1) in vitreous fluid samples from patients with proliferative diabetic retinopathy (PDR) and nondiabetic control patients. The difference between the two means was statistically significant at 5% level of significance.
Figure 2
Figure 2
Significant positive correlations between vitreous fluid levels of lysophosphatidic acid (LPA) and phosphatidic acid (PA) in vitreous samples from 25 proliferative diabetic retinopathy and 15 nondiabetic control patients (A) and soluble vascular cell adhesion molecule-1 (sVCAM-1) in vitreous samples from 22 proliferative diabetic retinopathy and 12 nondiabetic control patients (B).
Figure 3
Figure 3
Comparisons of mean band intensities for phospholipase A1A (PLA1A), acylglycerol kinase (AGK), sphingosine-1-phosphate receptor 1 (S1PR1) and sphingosine-1-phosphate lyase (SPL) in vitreous samples from proliferative diabetic retinopathy (PDR) patients (n = 16) and nondiabetic control patients (n = 16). A representative set of samples is shown. The difference between the two means was statistically significant at 5% level of significance.
Figure 4
Figure 4
Western blot analysis of phospholipase A2 (PLA2) and 5-lipoxygenase in serum samples from patients with proliferative diabetic retinopathy. A representative set of samples is shown. There is expression of PLA2 and 5-lipoxygenase in serum samples.
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References

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