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(Circulation Research. 2008;103:e118.)
© 2008 American Heart Association, Inc.

Letters to the Editor

Regulation of Vascular Endothelial Growth Factor A by Activating Transcription Factor 4

Steven F. Abcouwer, PhD

Associate Professor of Surgery, Cellular & Molecular Physiology, and Ophthalmology, Penn State University College of Medicine, Milton S. Hershey Medical Center, Hershey, PA 17033-0850, E-mail sabcouwer@psu.edu

C. Nathaniel Roybal, MD/PhD

UCLA Jules Stein EyeSTAR Residency Fellowship in Ophthalmology, Photoreceptor Biochemistry Lab, Jules Stein Eye Institute, Los Angeles, CA 90095

An extract of the first 100% of the full text is provided, because this article has no abstract.

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).

Disclosures

None.

1. 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.[Abstract/Free Full Text]

2. 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.[Abstract/Free Full Text]

3. 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.[Abstract/Free Full Text]

4. 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.[Abstract/Free Full Text]

5. 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.[Abstract/Free Full Text]

6. Chin MT. ATF-4 and vascular injury: integration of growth factor signaling and the cellular stress response. Circ Res. 2008; 103: 331–333.[Free Full Text]