New anti-angiogenic compound based on chemically modified heparin

Area of Science:

• Ophthalmology
• Vascular Biology
• Pharmacology

Background:

• Angiogenesis, the formation of new blood vessels, is crucial for development but implicated in diseases like choroidal neovascularization (CNV).
• Heparin derivatives are explored for anti-angiogenic properties, necessitating investigation into novel modified forms.

Purpose of the Study:

• To evaluate the anti-angiogenic potential of N-desulfated Re-N-acetylated, a chemically modified heparin (mHep).
• To assess the effects of mHep on endothelial cell functions and in a model of choroidal neovascularization.

Main Methods:

• In vitro assays assessed endothelial cell proliferation, tube formation, and migration following mHep treatment.
• In vivo studies utilized laser-induced CNV in rats, with intravitreal injections of mHep and subsequent immunofluorescence analysis.

Main Results:

• mHep significantly inhibited endothelial cell proliferation, tube formation, and migration without affecting cell viability.
• In vivo, mHep treatment led to a statistically significant reduction in choroidal neovascularization area and perimeter compared to controls.

Conclusions:

• N-desulfated Re-N-acetylated (mHep) demonstrates potent anti-angiogenic, anti-proliferative, and anti-migratory effects.
• mHep exhibits negligible anticoagulant or hemorrhagic activity and no cytotoxicity to retinal cells.
• This modified heparin is a promising candidate for therapeutic strategies targeting choroidal neovascularization.