PNAS: Novel Function of VEGF-B as a Potent Antioxidant

Source: Zhongshan Ophthalmic Center
Written by: Zhongshan Ophthalmic Center
Edited by: Wang Dongmei

On September 24, 2018, an article titled “VEGF-B is a potent antioxidant” was published by Dr. Xuri Li’s team at the Zhongshan Ophthalmic Center (ZOC), Sun Yat-sen University (SYSU) in Guangzhou in the journal of Proc Natl Acad Sci U S A (PNAS)¹. In this article, a previously unrecognized novel function of VEGF-B as a robust antioxidant is unveiled.
 

Dr. Xuri Li (middle in the front) and her team at ZOC, SYSU
 

Although VEGF-B was discovered a long time ago in 1996, unlike VEGF-A, whose function has been extensively studied, the function of VEGF-B and the mechanisms involved remain poorly understood. VEGF-B is abundantly expressed in most types of cells and organs. It is therefore critical to have a better understanding of VEGF-B’s function and the underlying mechanisms.

In this work, Dr. Li’s team shows that VEGF-B up-regulates the expression of numerous key anti-oxidative genes, particularly Gpx1, in many cell types, and protects the cells from oxidative stress-induced cell death. Indeed, loss of Vegf-b by gene deletion increased the expression of many oxidative genes and led to retinal degeneration in mice; and VEGF-B protein treatment rescued degenerating retinal cells from death in a retinitis pigmentosa model. Importantly, loss of Gpx1 activity largely diminished the anti-oxidative effect of VEGF-B both in vivo and in vitro, demonstrating that Gpx1 is at least one of the critical downstream effectors of VEGF-B.

Apart from the above findings, Dr. Li’s team has also shown previously that VEGF-B is a potent inhibitor of apoptosis by suppressing the expression of BH3-only protein genes and other apoptosis- and cell death-related genes². Consistently, VEGF-B treatment rescued the endangered neurons from apoptosis in both retina and brain in different disease models².

Together, these findings show that VEGF-B is the first member from the VEGF family to be recognized as an important regulator of anti-oxidation and anti-apoptotic pathways. Given that oxidative stress and apoptosis are crucial factors in numerous human diseases, VEGF-B may have important therapeutic value for the treatment of oxidative stress- and apoptosis-related diseases and aging.

Reference
1. VEGF-B is a potent antioxidant. Arjunan P, Lin X, Tang Z, Du Y, Kumar A, et al, Liu Y, Zhao C, and Xuri Li, PNAS, Sept. 24 2018
    http://www.pnas.org/content/early/2018/09/21/1801379115

2. VEGF-B inhibits apoptosis via VEGFR-1-mediated suppression of the expression of BH3-only protein genes in mice and rats. Li Y, Zhang F, Nagai N, Tang Z, Zhang S., et al, Heldin C H, Xuri Li, J Clin Invest., 118(3):913-23, 2018.