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PARP1 deficiency protects against hyperglycemia-induced neointimal hyperplasia by upregulating TFPI2 activity in diabetic mice.

Abstract
Diabetes mellitus (DM) promotes neointimal hyperplasia, characterized by dysregulated proliferation and accumulation of vascular smooth muscle cells (VSMCs), leading to occlusive disorders, such as atherosclerosis and stenosis. Poly (ADP-ribose) polymerase 1 (PARP1), reported as a crucial mediator in tumor proliferation and transformation, has a pivotal role in DM. Nonetheless, the function and potential mechanism of PARP1 in diabetic neointimal hyperplasia remain unclear. In this study, we constructed PARP1 conventional knockout (PARP1-/-) mice, and ligation of the left common carotid artery was performed to induce neointimal hyperplasia in Type I diabetes mellitus (T1DM) mouse models. PARP1 expression in the aorta arteries of T1DM mice increased significantly and genetic deletion of PARP1 showed an inhibitory effect on the neointimal hyperplasia. Furthermore, our results revealed that PARP1 enhanced diabetic neointimal hyperplasia via downregulating tissue factor pathway inhibitor (TFPI2), a suppressor of vascular smooth muscle cell proliferation and migration, in which PARP1 acts as a negative transcription factor augmenting TFPI2 promoter DNA methylation. In conclusion, these results suggested that PARP1 accelerates the process of hyperglycemia-induced neointimal hyperplasia via promoting VSMCs proliferation and migration in a TFPI2 dependent manner.
AuthorsZhao-Yang Wang, Meng-Qi Guo, Qing-Ke Cui, Haitao Yuan, Shan-Ji Fu, Bin Liu, Fei Xie, Wen Qiao, Jie Cheng, Ying Wang, Ming-Xiang Zhang
JournalRedox biology (Redox Biol) Vol. 46 Pg. 102084 (10 2021) ISSN: 2213-2317 [Electronic] Netherlands
PMID34364219 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.
Chemical References
  • Lipoproteins
  • lipoprotein-associated coagulation inhibitor
Topics
  • Animals
  • Carotid Artery Injuries (pathology)
  • Cell Movement
  • Cell Proliferation
  • Cells, Cultured
  • Diabetes Mellitus, Experimental (genetics, pathology)
  • Disease Models, Animal
  • Hyperglycemia (genetics, pathology)
  • Hyperplasia (pathology)
  • Lipoproteins
  • Mice
  • Muscle, Smooth, Vascular (pathology)
  • Myocytes, Smooth Muscle (pathology)

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