Journal of Vascular Medicine & Surgery

Molecular mechanism and prevention of VEGF-induced micro-vascular leakage in the retina of diabetic mice

World Congress on Vascular Diseases, Medicine & Surgeons Summit

October 24-25, 2016 Chicago, USA

Kwon-Soo Ha

Kangwon National University, South Korea

Posters & Accepted Abstracts: Vasc Med Surg

Abstract:

Diabetic retinopathy is predominantly caused by vascular endothelial growth factor (VEGF)-induced micro-vascular leakage; however, the underlying mechanism is unclear. Here, we demonstrated that hyperglycemia induced microvascular leakage by activating TGase2 and this vascular leakage was inhibited by C-peptide in diabetic retina. VEGF elevated TGase2 activity through sequential elevation of intracellular Ca2+ and reactive oxygen species (ROS) levels in endothelial cells. The TGase inhibitors cystamine and monodancylcadaverin or TGase2 siRNA prevented VEGF-induced stress fiber formation and vascular endothelial (VE)-cadherin disruption, which play a critical role in modulating endothelial permeability. C-peptide inhibited the VEGF-induced ROS generation, stress fiber formation and disassembly of vascular endothelial cadherin in endothelial cells. Intra-vitreal injection of C-peptide, two TGase inhibitors, or TGase2 siRNA successfully inhibited hyperglycemia-induced TGase activation and micro-vascular leakage in the retinas of diabetic mice. Thus, our findings suggest that C-peptide prevents VEGF-induced micro-vascular permeability by inhibiting ROS-mediated activation of TG2 in diabetic mice.

Biography :

Email: ksha@kangwon.ac.kr