Premium
The vicious cycle between transglutaminase 2 and reactive oxygen species in hyperglycemic memory–induced endothelial dysfunction
Author(s) -
Lee JeeYeon,
Lee YeonJu,
Jeon HyeYoon,
Han EunTaek,
Park Won Sun,
Hong SeokHo,
Kim YoungMyeong,
Ha KwonSoo
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201901358rr
Subject(s) - endothelial dysfunction , reactive oxygen species , oxidative stress , endothelium , cell adhesion molecule , medicine , apoptosis , endocrinology , diabetes mellitus , biology , microbiology and biotechnology , biochemistry
Clinical trials suggested that the vascular system can remember episodes of poor glycemic control through a phenomenon known as hyperglycemic memory (HGM). HGM is associated with long‐term diabetic vascular complications in type 1 and type 2 diabetes, although the molecular mechanism of that association is not clearly understood. We hypothesized that transglutaminase 2 (TGase2) and intracellular reactive oxygen species (ROS) play a key role in HGM‐induced vascular dysfunction. We found that hyperglycemia induced persistent oxidative stress, expression of inflammatory adhesion molecules, and apoptosis in the aortic endothelium of HGM mice whose blood glucose levels had been normalized by insulin supplementation. TGase2 activation and ROS generation were in a vicious cycle in the aortic endothelium of HGM mice and also in human aortic endothelial cells after glucose normalization, which played a key role in the sustained expression of inflammatory adhesion molecules and apoptosis. Our findings suggest that the TGase2‐ROS vicious cycle plays an important role in HGM‐induced endothelial dysfunction.—Lee, J.‐Y., Lee, Y.‐J., Jeon, H.‐Y., Han, E.‐T., Park, W. S., Hong, S.‐H., Kim, Y.‐M., Ha, K.‐S. The vicious cycle between transglutaminase 2 and reactive oxygen species in hyperglycemic memory–induced endothelial dysfunction. FASEB J. 33, 12655–12667 (2019). www.fasebj.org