Down‐regulation of Suv39h1 attenuates neointima formation after carotid artery injury in diabetic rats

Abstract

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.

miR-24 Alleviates MI/RI by Blocking the S100A8/TLR4/MyD88/NF-kB Pathway

“…Total protein was extracted from the infarcted border zone and analyzed by western blotting as previously described. 9 Briefly, the extracted proteins were separated by 10% sodium dodecyl sulfate-polyacrylamide gel electrophoresis and transferred onto nitrocellulose membranes. Nonspecific binding was blocked with 10% nonfat dry milk for 1.5 hours at room temperature.…”

KDM3A Inhibition Ameliorates Hyperglycemia-Mediated Myocardial Injury by Epigenetic Modulation of Nuclear Factor Kappa-B/P65

“…Increasing evidence indicates that DM-or HG-triggered histone methylation is a crucial feature for persistent and extensive hyperglycemiamediated cardiovascular injury. For instance, the histone methyltransferase SUV39H1-H3K9me3 pathway is a key factor that triggers the HG-mediated injury in VSMCs (22,46). The histone methyltransferase Set7-H3K4me1 pathway has been shown to participate in HG-mediated injury in aortic endothelial cells (47).…”

Chemokine‐like factor 1 (CKLF1) aggravates neointimal hyperplasia through activating the NF‐κB /VCAM‐1 pathway

“…Animals had free access to standard solid claviform food and autoclaved tap water. To simulate an angioplasty in rats, the carotid artery balloon‐injured models were performed with a 2.0‐mm diameter balloon (Medtronic, Dublin, Ireland) as described previously [16]. After balloon injury, rats were randomized into the four groups (five rats per group): Ad‐ CKLF1 , Ad‐ GFP , Ad‐ shCKLF1 and Ad‐ shRNA scramble .…”