Dataset Information

Suppression of circDcbld1 Alleviates Intimal Hyperplasia in Rat Carotid Artery by Targeting miR-145-3p/Neuropilin-1.

ABSTRACT: We replicated the rat common carotid artery (CCA) intima hyperplasia model and found the expression of a circular RNA, circRNA_009723 (circDcbld1), was markedly increased in the CCA with intimal hyperplasia. In vitro, the suppression of circDcbld1 in rat vascular smooth muscle cells (VSMCs) led the increase of contractile smooth muscle cell markers and the decrease of cell migration. In vivo, the injection of chemically modified circDcbld1 small interfering RNA (siRNA) lessened the formation of neointima in rat CCA after balloon injury. Further experiments proved that circDcbld1, as a competing endogenous RNA, interacted with miR-145-3p and upregulated the level of neuropilin-1 (Nrp1), thereby regulating the migration of VSMCs. In this study, we demonstrated a new mechanism by which circular RNA promotes intimal hyperplasia. We deem that intervention in the circDcbld1-miR-145-3p/Nrp1 pathway might be a feasible approach to alleviate the post-injury intimal hyperplasia.

SUBMITTER: Rong ZH

PROVIDER: S-EPMC6889766 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Suppression of circDcbld1 Alleviates Intimal Hyperplasia in Rat Carotid Artery by Targeting miR-145-3p/Neuropilin-1.

Rong Zhi-Hua ZH Chang Neng-Bin NB Yao Qing-Ping QP Li Tao T Zhu Xiao-Ling XL Cao Yu Y Jiang Mei-Jun MJ Cheng Yan-Shuang YS Jiang Rui R Jiang Jun J

Molecular therapy. Nucleic acids 20191028

We replicated the rat common carotid artery (CCA) intima hyperplasia model and found the expression of a circular RNA, circRNA_009723 (circDcbld1), was markedly increased in the CCA with intimal hyperplasia. In vitro, the suppression of circDcbld1 in rat vascular smooth muscle cells (VSMCs) led the increase of contractile smooth muscle cell markers and the decrease of cell migration. In vivo, the injection of chemically modified circDcbld1 small interfering RNA (siRNA) lessened the formation of ...[more]

PMID: 31778958

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Project description:Intimal hyperplasia (IH) is a prominent pathological event that occurs during in-stent restenosis and atherosclerosis. Ferroptosis, characterized by iron-dependent and lipid peroxidation, has become the recent focus of studies on the occurrence and progress of cardiovascular diseases. However, there are few studies on ferroptosis and IH. Therefore, we aimed to identify and validate ferroptosis-related markers in IH to explore new possibilities for IH diagnosis and treatment. The IH microarray dataset (GSE182291) was downloaded from the Gene Expression Omnibus (GEO) database and ferroptosis-related genes (FRGs) were obtained from the FerrDb databases. The differentially expressed genes (DEGs) were analyzed using the GEO2R. Overlapping was performed to identify the ferroptosis-related DEGs among the DEGs and FRGs. Then, clustering, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and protein-protein interaction (PPI) analyses were performed. Subsequently, the hub genes were identified using Cytoscape and hub gene-transcription factors and hub gene-microRNA networks were constructed. Finally, real-time qPCR (RT-qPCR) and immunohistochemistry (IHC) were used to verify the mRNA and protein levels of the hub FRGs in IH. Thirty-four FRGs showing significantly different expression were identified from a total of 1,197 DEGs 2 days after ligation; 31 FRGs were selected from a total of 1,556 DEGs 14 days after ligation. The GO and KEGG analyses revealed that these 34 ferroptosis-related DEGs identified 2 days after ligation were mainly enriched in the basolateral plasma membrane, ferroptosis, lipid and atherosclerosis, and IL-17 signaling pathways. The 31 ferroptosis-related DEGs in endometrial hyperplasia identified 14 days after ligation were mainly enriched in response to oxidative stress, ferroptosis, tumor necrosis factor signaling pathway, and lipid and atherosclerosis. Five hub FRGs (Il1b, Ptgs2, Cybb, Cd44, and Tfrc) were identified using PPI networks; four hub FRGs (Il1b, Ptgs2, Cybb, and Cd44) were validated to be upregulated 2 and 14 days after ligation using RT-qPCR and show significantly different expression 14 days after ligation via IHC. Our findings verify the expression of hub DEGs related to ferroptosis in IH and elucidate the potential relationship between ferroptosis and IH, providing more evidence about the vital role of ferroptosis in IH.

Project description:In-stent restenosis (ISR) is the main factor affecting the outcome of percutaneous coronary intervention (PCI), and its main pathological feature is neointimal hyperplasia. Huotan Jiedu Tongluo decoction (HTJDTLD) is an effective traditional Chinese medicine (TCM) prescription for the treatment of vascular stenosis diseases. However, the precise anti-ISR mechanism of HTJDTLD remains unclear. Here, we investigated whether HTJDTLD can inhibit the excessive activation of endoplasmic reticulum stress (ERS) and reduce the level of autophagy factors through regulating the PERK-eIF2α-ATF4 pathway, thereby inhibiting the proliferation of the intima of blood vessels damaged by balloon injury (BI) and preventing the occurrence of ISR. In this study, a 2F Fogarty balloon was used to establish a common carotid artery (CCA) BI model in male Sprague-Dawley rats. Then, HTJDTLD (16.33 g/kg/d) or atorvastatin (1.19 mg/kg/d) was administered by gavage. Four weeks later, hematoxylin-eosin (HE) and Masson staining of the injured CCA were performed to observe the histological changes in the CCA. Immunohistochemistry (IHC) was used to assess the proliferation and dedifferentiation of vascular smooth muscle cells (VSMCs) in the CCA. Western blotting and RT-PCR were used to measure the expression of ERS- and autophagy-related proteins and mRNAs in the CCA. The results indicated that HTJDTLD significantly alleviated BI-induced carotid artery intimal hyperplasia and fibrosis and reduced the neointimal area (NIA) and NIA/medial area (MA) ratio. In addition, HTJDTLD inhibited the proliferation and dedifferentiation of VSMCs, reduced the expression of proliferating cell nuclear antigen (PCNA), and increased the smooth-muscle-α-actin- (SMα-actin-) positive area. HTJDTLD also significantly reduced the expression of the ERS-related factors: GRP78, p-PERK/PERK, p-eIF2α/eIF2α, ATF4, and CHOP. In addition, the expression of the autophagy-related factors, Beclin1, LC3B, and ATG12, was significantly decreased. In addition, in vitro experiments showed that HTJDTLD inhibited the above-mentioned ERS signal molecules in human umbilical vein endothelial cells (HUVEC) and rat aortic smooth muscle cells (A7R5) induced by tunicamycin (TM) and played a crucial role in protecting cells from damage. HTJDTLD may be a very promising drug for the treatment of ISR.

Dataset Information

Suppression of circDcbld1 Alleviates Intimal Hyperplasia in Rat Carotid Artery by Targeting miR-145-3p/Neuropilin-1.

Publications

Suppression of circDcbld1 Alleviates Intimal Hyperplasia in Rat Carotid Artery by Targeting miR-145-3p/Neuropilin-1.

Similar Datasets

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