Cilengitide Inhibits Neovascularization in a Rabbit Abdominal Aortic Plaque Model by Impairing the VEGF Signaling

Area of Science:

• Cardiovascular Research
• Integrin Signaling
• Angiogenesis Inhibition

Background:

• Cilengitide selectively inhibits αvβ3 and αvβ5 integrins.
• Investigated cilengitide's impact on abdominal aortic plaque neovascularization in rabbits.
• Explored its antiangiogenic mechanism on human umbilical vein endothelial cells (HUVECs).

Purpose of the Study:

• To evaluate cilengitide's effect on abdominal aortic plaque neovascularization in a rabbit model.
• To elucidate the antiangiogenic mechanism of cilengitide on HUVECs.
• To assess cilengitide's impact on plaque size, vascularity, and key molecular pathways.

Main Methods:

• Established abdominal aortic plaque model in rabbits, treated with varying cilengitide doses or saline.
• Utilized conventional and contrast-enhanced ultrasound (CEUS) for vascular assessment.
• Conducted in vitro studies on HUVECs assessing proliferation, migration, apoptosis, and tube formation, alongside molecular pathway analysis (VEGF, integrins, Ras/ERK/AKT).

Main Results:

• Cilengitide treatment reduced plaque size and eccentricity index in rabbits.
• Inhibited plaque neovascularization, VEGF, and integrin expression.
• In vitro, cilengitide suppressed HUVEC proliferation, migration, and tube formation without inducing apoptosis.
• Significantly inhibited the Ras/ERK/AKT pathway in HUVECs.

Conclusions:

• Cilengitide effectively inhibits abdominal aortic plaque growth by targeting angiogenesis.
• Blocks VEGF-mediated angiogenic effects on HUVECs.
• Demonstrates therapeutic potential in reducing atherosclerotic plaque neovascularization.