Regulation of Vascular Endothelial Growth Factor A by Activating Transcription Factor 4
To the Editor:
In a recent article published in Circulation Research, Malabanan et al demonstrated that expression of vascular endothelial growth factor (VEGF)-A in response to fibroblast growth factor-2 is regulated by activating transcription factor (ATF)4.1 Although these authors never explicitly stated that theirs was the first and only study demonstrating that VEGF-A is ATF4-responsive, they failed to acknowledge the contributions of 4 previous publications demonstrating regulation of VEGF-A by ATF4.1–5 Although the authors stated that the existence of an ATF4 binding site in the VEGF-A gene was previously demonstrated, they neglected to mention that any previous study had ever established a role of ATF4 in the control of VEGF-A transcription. Furthermore, an accompanying review by Chin accounted how Malabanan et al demonstrated this regulation, while similarly failing to acknowledge that this aspect of their work was simply confirmatory.6
Sources of Funding
Supported by the American Health Assistance Foundation (SFA) and the Juvenile Diabetes Research Foundation (SFA).
Malabanan KP, Kanellakis P, Bobik A, Khachigian LM. Activation transcription factor-4 induced by fibroblast growth factor-2 regulates vascular endothelial growth factor-A transcription in vascular smooth muscle cells and mediates intimal thickening in rat arteries following balloon injury. Circ Res. 2008; 103: 378–387.
Chakraborty G, Jain S, Kundu GC. Osteopontin promotes vascular endothelial growth factor-dependent breast tumor growth and angiogenesis via autocrine and paracrine mechanisms. Cancer Res. 2008; 68: 152–161.
Oskolkova OV, Afonyushkin T, Leitner A, von Schlieffen E, Gargalovic PS, Lusis AJ, Binder BR, Bochkov VN. ATF4-dependent transcription is a key mechanism in VEGF up-regulation by oxidized phospholipids: critical role of oxidized sn-2 residues in activation of unfolded protein response. Blood. 2008; 112: 330–339.
Roybal CN, Hunsaker LA, Barbash O, Vander Jagt DL, Abcouwer SF. The oxidative stressor arsenite activates vascular endothelial growth factor mRNA transcription by an ATF4-dependent mechanism. J Biol Chem. 2005; 280: 20331–20339.
Roybal CN, Yang S, Sun CW, Hurtado D, Vander Jagt DL, Townes TM, Abcouwer SF. Homocysteine increases the expression of vascular endothelial growth factor by a mechanism involving endoplasmic reticulum stress and transcription factor ATF4. J Biol Chem. 2004; 279: 14844–14852.
Chin MT. ATF-4 and vascular injury: integration of growth factor signaling and the cellular stress response. Circ Res. 2008; 103: 331–333.