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C. V. Regatieri, J. L. Dreyfuss, M. A. Lima, S. Chavante, H. B. Nader, M. E. Farah; Anti-Angiogenic Effect of a Heparin-Like Glycosaminoglycan Isolated From a Marine Shrimp. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3352.
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It has been shown that a heparin-like glycosaminoglycan obtained from shrimp cephalotorax (Litopenaeus vannamei) is capable to modulate inflammatory responses without interfering on hemostasis. Besides it reduced bleeding potential and anticoagulant activity in vitro, the shrimp heparin-like compound is able to reduce the activity of matrix metalloproteinases. Thus the objective of this study was to evaluate the anti-angiogenic effects of this new compound on an " in vitro" and "in vivo" models.
The ability of endothelial cells form capillary-like structures "in vitro" when plated on top of a reconstituted basement membrane extracellular matrix (Matrigel) was investigated in cells treated with the heparin-like compound (0.09, 0.9 and 9 µg/mL). The cytotoxicity of this compound was evaluated by MTT test in retinal pigmented epithelial cells (ARPE-19) and endothelial cell cultures. The "in vivo" model to evaluate the anti-angiogenic effect of this compound was the laser-induced choroidal neovascularization (CNV) in rats. The CNV was induced using argon laser, and at the end of laser session, saline or heparin-like glycosaminoglycan were injected intravitreously in the 4 groups of animals (laser, and laser with 0.09, 0.9 and 9 µg/mL of heparin-like glycosaminoglycan). After three weeks, the eyes were enucleated and immunofluorescence was performed (flatmount) using anti-von Willebrand factor, a marker for endothelial cells.
All three tested doses of the heparin-like glycosaminoglycan induced a significant decrease (p<0.05) in total length of tubes formed by endothelial cells in Matrigel. Immunofluorescence analysis showed significant reduction in CNV lesion area of all groups treated with heparin-like glycosaminoglycan. The regression observed was 28%, 53% and 41% in 0.09, 0.9 and 9 µg/mL treated groups, respectively (P<0.0001). No cytotoxic effect was detected in ARPE-19 or endothelial cell culture.
Intravitreal injection of the the heparin-like glycosaminoglycan from a marine shrimp significantly reduces the CNV lesion area. The optimal dosage to reduce angiogenesis was 0.9 µg/mL and it was no cytotoxic effect in ARPE-19 cells or endothelial cells. These results demonstrated a new useful antiangiogenic compound that can be used as a therapy to control neovascularization.
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