PARP1 deficiency protects against hyperglycemia-induced neointimal hyperplasia by upregulating TFPI2 activity in diabetic mice.
PARP1 deficiency protects against hyperglycemia-induced neointimal hyperplasia by upregulating TFPI2 activity in diabetic mice.
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DOI：
10.1016/j.redox.2021.102084
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发表时间：
2021-10
期刊：
影响因子：
11.4
通讯作者：
Zhang MX
中科院分区：
文献类型：
--
作者：
Wang ZY;Guo MQ;Cui QK;Yuan H;Shan-Ji Fu;Liu B;Xie F;Qiao W;Cheng J;Wang Y;Zhang MX
糖尿病（DM）促进新生内膜增生，其特征在于血管平滑肌细胞（VSMC）的增殖和积聚失调，导致闭塞性疾病，如动脉粥样硬化和狭窄。多聚腺苷二磷酸核糖聚合酶1（Poly（ADP-ribose）polymerase 1，PARP 1）在糖尿病的发病中起着重要作用。尽管如此，PARP 1在糖尿病新生内膜增生中的功能和潜在机制仍不清楚。在本研究中，我们构建了PARP 1常规敲除（PARP 1 −/−）小鼠，并在I型糖尿病（T1 DM）小鼠模型中进行左颈总动脉结扎以诱导新生内膜增生。T1 DM小鼠主动脉PARP 1表达显著增加，PARP 1基因缺失对新生内膜增生有抑制作用。此外，我们的研究结果表明，PARP 1通过下调组织因子途径抑制物（TFPI 2）增强糖尿病新生内膜增生，TFPI 2是血管平滑肌细胞增殖和迁移的抑制因子，其中PARP 1作为负转录因子增强TFPI 2启动子DNA甲基化。总之，这些结果表明，PARP 1通过促进VSMCs增殖和迁移以TFPI 2依赖的方式加速高血糖诱导的新生内膜增生的过程。
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.
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影响因子：
5.3
作者：
Higashikata, T;Yamagishi, M;Akamoto, A
通讯作者：
Akamoto, A
DOI：
10.1161/01.atv.17.10.2238
发表时间：
1997-10-01
影响因子：
8.7
作者：
Kumar, A;Lindner, V
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影响因子：
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影响因子：
78.8
作者：
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通讯作者：
van Engeland, Manon
影响因子：
5.9
作者：
Son M;Oh S;Jang JT;Park CH;Son KH;Byun K
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