PARP1 deficiency protects against hyperglycemia-induced neointimal hyperplasia by upregulating TFPI2 activity in diabetic mice
Zhao-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
Affiliations
Zhao-yang Wang
Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China; Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
Meng-qi Guo
Department of Cardiology, the Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
Qing-ke Cui
Department of Neurosurgery, Liaocheng People's Hospital, Liaocheng, Shandong, China
Haitao Yuan
Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
Shan-ji Fu
Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, China
Bin Liu
Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
Fei Xie
Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
Wen Qiao
Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
Jie Cheng
Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
Ying Wang
Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China; Corresponding author. Qilu Hospital, Cheeloo College of Medicine, Shandong University, No.107, Wen Hua Xi Road, Jinan, Shandong, 250012, China.
Ming-xiang Zhang
Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China; Corresponding author. Qilu Hospital, Cheeloo College of Medicine, Shandong University, No.107, Wen Hua Xi Road, Jinan, Shandong, 250012, China.
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.
