Journal article

Role of the eNOS-NO System in Regulating the Antiproteinuric Effects of VEGF Receptor 2 Inhibition in Diabetes

Andrew Advani, Kim A Connelly, Suzanne L Advani, Kerri Thai, Yuan Zhang, Darren J Kelly, Richard E Gilbert



Subtle perturbations in intraglomerular VEGF/VEGFR-2 signaling or in the influencing microenvironment can profoundly affect renal function, resulting in the apparently paradoxical observation that VEGF blockade attenuates proteinuria development in experimental diabetes despite exerting the opposite effect under other circumstances. In the present study, we sought to explore the role of eNOS-NO activity in regulating the differential response to VEGF blockade in the diabetic and nondiabetic settings. In a rodent model of accelerated renal injury, the transgenic (mRen-2)27 (Ren-2) rat, VEGFR-2 inhibition with the small molecule vandetanib resulted in an increase in urine protein excretion pre..

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Funding Acknowledgements

The authors thank Bailey Stead, Golam Kabir, Katrina Zefkic, Christine Kuliszewski, Marianna Pacheco, and Jemma Court for their excellent technical assistance. Dr. Andrew Advani is a Canadian Diabetes Association Clinician Scientist, Dr. Richard E. Gilbert is a Canada Research Chair in Diabetes Complications, and this work was supported thanks, in part, to the Canadian Diabetes Association and the Canada Research Chair Program. Dr. Kim A. Connelly was supported by a Clinician Scientist Award from the Heart and Stroke Foundation of Ontario. These studies were supported by an Operating Grant from the Canadian Diabetes Association to Dr. Andrew Advani and a CIHR Grant to Dr. Richard E. Gilbert.