Levels and Effects of Nogo‐B in Patients With Type 2 Diabetes or Hyperglycemic HUVEC Model

ABSTRACT Background There is still a lack of enough evidence about Nogo‐B levels and vascular complications in patients with type 2 diabetes. Our first aim was to assess the levels of Nogo‐B in type 2 diabetes mellitus (T2DM) patients with or without vascular complications (VC). Our second aim was to determine the mechanism by which Nogo‐B may protect vasculature using a hyperglycemic HUVEC model. Methods Sera or samples of patients with T2DM and subjects without diabetes were collected from the First or Second Affiliated Hospital of Chongqing Medical University. Human umbilical endothelial cells (HUVECs) were purchased and treated with high glucose (HG) and/or cholesterol (C) before and after Nogo‐B knockdown or overexpression. Graphpad and SPSS version 27 software were used for statistical analyses. Results T2DM patients with vascular complications (DM + VC) displayed significantly lower levels of Nogo‐B when compared with T2DM patients without VC (DM) or subjects without diabetes (NC) (p < 0.001). In addition, lower levels of Nogo‐B were independently associated with diabetes and/or VC in T2DM patients. Nogo‐B overexpression reduced the expression of mesenchymal markers (α‐SMA and Collagen‐1), TGF‐β1 and P‐smad2/3, while increasing the expression of endothelial markers (CD31, eNOS and VWF) in HUVECs treated with HG and/or C. Conclusion Our study has proved that lower levels of Nogo‐B are independently associated with VC in T2DM patients. In an in vitro model, Nogo‐B alleviates endothelial cell injury by affecting TGF‐β signalling. Further studies are still needed to support or verify our findings.