Letter by Wu et al Regarding Article, “Anti-Inflammatory Actions of Soluble Ninjurin-1 Ameliorate Atherosclerosis”

We read with great interest the recent article by Jeon et al, 1 in which they revealed that Ninj1 (nerve injury-induced protein-1) is a matrix metalloproteinase 9 substrate, and the absence of Ninj1 exerts a proinflammatory effect by enhancing mitogen-activated protein kinase signaling and blocking the phosphoinositide 3-kinase/protein kinase B pathway in macrophages.They further showed that soluble Ninj1-mimetic peptides acted as anti-inflammatory mediators of macrophages and attenuated monocyte recruitment and atherosclerosis.Their results showed the important role of the soluble form of an adhesion molecule as a therapeutic target for atherosclerosis.However, there are some aspects that, in our opinion, need further research.A previous study described that Ninj1 reduced leukocyte recruitment into lesion sites and exerted an anti-inflammatory effect, 2 and another study showed Ninj1 mediated the activation of mitogen-activated protein kinase signaling and the inhibition of phosphoinositide 3-kinase/protein kinase B signaling, 3 which were at opposite poles of this article.Therefore, more studies should be performed to explore the reason for the differences.In addition, a previous study showed that Ninj1 was expressed in endothelial cells and mediated endothelial dysfunction.3 It would be interesting to explore the function of endothelium-derived Ninj1 in atherosclerosis.Ninj1 also showed a high expression in hepatocellular carcinoma 4 and exerted its oncogenic function by repressing p53-dependent growth suppression.5 Thus, the safety of soluble Ninj1-mimetic peptides in treating atherosclerosis also needs further research.