Down‐regulation of Suv39h1 attenuates neointima formation after carotid artery injury in diabetic rats
Down‐regulation of Suv39h1 attenuates neointima formation after carotid artery injury in diabetic rats
复制标题
DOI：
10.1111/jcmm.14809
复制
发表时间：
2019-11
影响因子：
5.3
通讯作者：
Jing Zhang;Jian Yang;Changwu Xu;Qi Hu;Jun Hu;J. Chen;Hong Jiang
中科院分区：
文献类型：
--
作者：
Jing Zhang;Jian Yang;Changwu Xu;Qi Hu;Jun Hu;J. Chen;Hong Jiang
糖尿病患者发生血管并发症的风险增加。suv 39 h1是一种组蛋白甲基转移酶，对糖尿病心肌损伤具有保护作用。本研究旨在探讨Suv 39 h1对糖尿病大鼠血管损伤后新生内膜形成的影响及其机制。在这项研究中，我们产生了表达Suv 39 h1的腺病毒以及表达Suv 39 h1靶向shRNA的慢病毒，并评估了Suv 39 h1在糖尿病条件下血管平滑肌细胞（VSMC）中的意义。在体外，我们研究了增殖和迁移行为，以及潜在的信号转导机制，在VSMCs响应于高糖治疗。在体实验中，采用链脲佐菌素诱导SD大鼠糖尿病，建立颈总动脉球囊损伤模型。Suv 39 h1在高糖条件下促进VSMC增殖和迁移是必要的，也是充分的。我们观察到细胞内信号分子的相应变化，包括补体C3和磷酸化ERK 1/2。然而，上调或下调Suv 39 h1，磷p38水平没有受到显著影响。结论：糖尿病大鼠颈动脉损伤后，Suv 39 h1过表达可加速新生内膜的形成，而Suv 39 h1敲低可减少新生内膜的形成。使用微阵列分析，我们发现改变体内Suv 39 h1水平显著改变了介导不同生物学过程和分子功能的无数基因的表达。本研究揭示了Suv 39 h1在糖尿病血管平滑肌细胞中的新作用，并提示其作为糖尿病血管损伤治疗靶点的潜在作用。
Patients with diabetes have an increased risk of vascular complications. Suv39h1, a histone methyltransferase, plays a protective role against myocardial injury in diabetes. Herein, we intend to explore whether Suv39h1 could affect neointimal formation after vascular injury in diabetic rats and reveal the underlying mechanism. In this study, we generated adenovirus expressing Suv39h1 as well as lentivirus expressing Suv39h1‐targeting shRNA and evaluated the significance of Suv39h1 in vascular smooth muscle cells (VSMCs) under diabetic conditions. In vitro, we examined proliferative and migratory behaviours as well as the underlying signalling mechanisms in VSMCs in response to high glucose treatment. In vivo, we induced diabetes in SD rats with streptozocin and established the common carotid artery balloon injury model. Suv39h1 was found to be both necessary and sufficient to promote VSMC proliferation and migration under high glucose conditions. We observed corresponding changes in intracellular signalling molecules including complement C3 and phosphor‐ERK1/2. However, either up‐regulating or down‐regulating Suv39h1, phosphor‐p38 level was not significantly affected. Consistently, Suv39h1 overexpression led to accelerated neointima formation, while knocking down Suv39h1 reduced it following carotid artery injury in diabetic rats. Using microarray analyses, we showed that altering the Suv39h1 level in vivo dramatically altered the expression of myriad genes mediating different biological processes and molecular function. This study reveals the novel role of Suv39h1 in VSMCs of diabetes and suggests its potential role as a therapeutic target in diabetic vascular injury.