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Faizah N Bhatti, Annette Linens; Effect of Surfactant Protein A on Vascular Function and Gene Profiling In Human Retinal Endothelial Cells. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):953.
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We have previously shown that Surfactant protein A (SP-A) SP-A modulates human retinal endothelial cell function in vitro and showed a decrease in neovascularization in SP-A-/- mice in the oxygen induced retinopathy (OIR) model. We hypothesize that SP-A decreases inflammatory signals and alters the expression of angiogenic factors in retinal microvascular endothelial cells. In order to test this hypothesis, human retinal endothelial cells (HREC’s) in culture were treated with purified human SP-A (hSP-A) protein. Expression of angiogenic and inflammatory mediators was then tested by real time Profiler PCR array.
HREC's were cultured and then treated with either 10 ug/ml of human purified SP-A protein (hSP-A) or control media for 6 hours. HREC function was then quantified using migration, proliferation and tube formation assays. RT-PCR array was then performed on the SP-A treated HREC's for 84 angiogenesis specific genes.<br />
HREC proliferation, migration and tube formation were significantly impaired after treatment with SP-A. After RT-PCR, genes were divided into three groups, those with an increase, decrease and the third group with no significant change. Genes with significant increases included: EPH receptor B4, Chemokine ligand 11, Endoglin, Collagen type XVIII, α1 and Cadherin 5, type 2 [vascular endothelium]. Genes with significant decrease included the following: Interleukin 8; Epidermal growth factor; Plasminogen activator, urokinase; TIMP metallopeptidase inhibitor 1. Gene pathways were arranged into three major categories: related to endothelial cell function, inflammation and oxidative stress. Surprisingly, specific well known genes involved in angiogenesis and oxygen induced damage were not changed e.g., VEGF-A, VEGF-B, VEGF-C, Hif1-alpha and Notch 4.
This data shows that several novel pathways are involved in the signaling pathways involving SP-A mediated changes in blood vessel growth and neovascularization. These pathways now need further elucidation and study to determine where SP-A function may be altered early enough in order to protect against the development of neovascularization in ROP.
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