Comment on “Vascular Endothelial Growth Factor (VEGF) as a Vital Target for Brain Inflammation during the COVID-19 Outbreak”

Abstract

Metrics & MoreArticle Recommendations D r. Yin and colleagues discussed the possible role of vascular endothelial growth factor (VEGF) in COVD-19-related brain inflammation. The authors claimed that the role of VEGF in COVID-19-related brain inflammation may be mediated through angiopoietins. 1 Although we agree that VEGF may play an important role in the development of cytokine storm in COVID-19-related brain inflammation, the authors mistakenly used angiopoietin and angiotensin interchangeably, and this may confuse the reader. Specifically, the authors used the abbreviation Ang II for angiopoietin 2; however, Ang II is the abbreviation for angiotensin II, and Ang 2 is the correct abbreviation for angiopoietin 2. 2−4 The authors also incorrectly stated that angiopoietin 2, which was abbreviated Ang II in the abstract and subsequent sections of the article, was the product of the SARS-CoV-2-attacking target, angiotensin-converting enzyme 2 (ACE2). In reality, angiotensin II (Ang II) is the product of ACE2; therefore, SARS-CoV-2 actually targets angiotensin II (Ang II), not angiopoietin 2 (Ang 2). 2−4 Further, the authors mentioned that exogenous VEGF and Ang II (alone or combination) facilitated the release of inflammatory cytokines, such as IL-8 and IL-6. The cited reference reports that angiopoietin 2 (Ang 2) and not Ang II is induced by VEGF and facilitates the release of IL-8 and IL-6. 5 On the basis of the context of the article, it may be interpreted that the authors were referring to angiopoietin 2 when they used the abbreviation Ang II; however, this abbreviation was also used for angiotensin II in subsequent text and figures. The authors also conclude that angiotensin II (Ang II) plays a role in the upregulation of TNF-α, IL-1β, IL-6, IL-8, and ICAM-1 in brain inflammation through a vicious cycle. Nonetheless, the literature that was referenced did not support this claim; instead, it described the role of angiopoietin 2 in the upregulation of cytokines. Therefore, it is not clear if the authors have a reference for this conclusion that was unintentionally excluded or if they inadvertently used the previous reference that was used to describe the role of angiopoietin to support this claim.According to findings from previous studies, we believe that VEGF may play a role in the development of cytokine storm and that a biological correlation may exist between angiotensin II (Ang II), VEGF, and angiopoietin 2 (Ang 2). For example, studies have revealed that angiotensin II induces angiopoietin 2 and VEGF, and angiotensin II has also been implicated in angiogenesis. 6−9 Additionally, angiotensin II promotes the inflammation and release of various inflammatory mediators. 10−12 However, we have yet to uncover evidence that supports the role of VEGF in the activation of angiotensin II signaling and COVID-19-related brain inflammation that was described in this article.