scholarly journals Silencing epigenetic writer DOT1L attenuates intimal hyperplasia

2019 ◽  
Author(s):  
Yitao Huang ◽  
Go Urabe ◽  
Mengxue Zhang ◽  
Jing Li ◽  
Bowen Wang ◽  
...  
Keyword(s):  
Balloon Angioplasty ◽  
Intimal Hyperplasia ◽  
Carotid Arteries ◽  
Selective Inhibitor ◽  
Epigenetic Therapy ◽  
Post Injury ◽  
Histone Methyltransferases ◽  
Telomeric Silencing ◽  
H3k79 Methylation

AbstractObjectiveHistone methyltransferases are emerging targets for epigenetic therapy. DOT1L (disruptor of telomeric silencing 1-like) is the H3K79 methylation writer. We investigated its role in the development of intimal hyperplasia (IH).Approach and ResultsIH was induced via balloon angioplasty in rat carotid arteries. DOT1L and its catalytic products H3K79me2 and H3K79me3 (immunostaining) increased by 4.69 ±0.34, 2.38 ±0.052, and 3.07 ±0.27 fold, respectively, in injured (versus uninjured) carotid arteries at post-injury day 7. DOT1L silencing via shRNA-lentivirus infusion in injured arteries reduced DOT1L, H3K79me2, and IH at day 14 by 54.5%, 37.1%, and 76.5%, respectively. Moreover, perivascular administration of a DOT1L-selective inhibitor (EPZ5676) reduced H3K79me2, H3K79me3, and IH by 56.1%, 58.6%, and 39.9%, respectively.ConclusionsDOT1L inhibition mitigates the development of IH.

scholarly journals Sophocarpine Alleviates Injury-Induced Intima Hyperplasia of Carotid Arteries by Suppressing Inflammation in a Rat Model

2021 ◽  
Vol 10 (22) ◽  
pp. 5449
Author(s):  
Genhuan Yang ◽  
Rong Zeng ◽  
Xitao Song ◽  
Changwei Liu ◽  
Leng Ni
Keyword(s):  
Carotid Artery ◽  
Balloon Angioplasty ◽  
Intimal Hyperplasia ◽  
Carotid Arteries ◽  
Control Group ◽  
Therapeutic Effects ◽  
Balloon Injury ◽  
Protein Levels ◽  
Injury Group ◽  
Tnf Α

Introduction: Balloon angioplasty is a commonly applied procedure for treating atherosclerotic vascular diseases. However, the maintenance of long-term lumen patency is relatively difficult due to the occurrence of restenosis. Previous research has shown that the occurrence of vascular wall inflammation is associated with higher rates of restenosis. Sophocarpine (SPC) can exert various therapeutic effects such as anti-oxidation, anti-inflammation, anti-tumor, antivirus and immune regulation. This study aimed to investigate whether SPC can alleviate intimal hyperplasia following balloon injury in a rat carotid artery model. Methods: Twenty Sprague–Dawley rats were randomly assigned to four groups: (i) control, (ii) balloon injury, (iii) balloon injury followed by saline injection, and (iv) balloon injury followed by SPC administration. Each group contained five rats. A high-pressure balloon of 3 mm × 20 mm was placed in the carotid artery. The balloon was inflated to a pressure of 8 atmospheres to carry out rat carotid artery balloon injury model. The areas of neointimal and media were determined by Verhoeff_Van Gieson staining, and the intima-to-media (I:M) ratios were subsequently evaluated. After that, the protein levels of IL-6, IL-1β, MCP-1, NF-κB, TNF-α, VCAM-1, ICAM-1 and eNOS were measured. Results: The ratio of I:M was remarkably higher in the balloon injury group than in the control group (p < 0.01). SPC could significantly decrease the ratio of I:M compared with the balloon injury group (p < 0.01). Besides, the protein levels of IL-6, IL-1β, MCP-1, NF-κB, TNF-α, ICAM-1 and VCAM-1 were increased in rat carotid arteries exposed to balloon injury (p < 0.01), and treatment with SPC could attenuate these effects (p < 0.05). Furthermore, balloon injury inhibited the protein expression of eNOS (p < 0.01), and SPC could elevate its level (p < 0.05). Conclusions: SPC could alleviate an intimal hyperplasia in balloon-injured carotid artery, and the mechanisms underlying this protective effect might be due to its inhibitory potency against inflammation signals. Our study also implies the potential applicability of SPC in treating restenosis after balloon angioplasty.

scholarly journals Intimal Hyperplasia in Loop-Injured Carotid Arteries Is Attenuated in Transglutaminase 2-Null Mice

2014 ◽  
Vol 29 (3) ◽  
pp. 363 ◽  
Author(s):  
Seung-Kee Min ◽  
Sang-Il Min ◽  
Eui Man Jeong ◽  
Sung-Yup Cho ◽  
Jongwon Ha ◽  
...  
Keyword(s):  
Intimal Hyperplasia ◽  
Carotid Arteries ◽  
Transglutaminase 2

scholarly journals Cilostazol as a noninferiority pharmacologic option to paclitaxel in early intimal hyperplasia inhibition after venous balloon angioplasty in a rabbit model: a preliminary study

2020 ◽  
Vol 1 ◽  
pp. 200-206
Author(s):  
Rodrigo Lozano-Corona ◽  
Hugo Laparra-Escareno ◽  
Javier E. Anaya-Ayala ◽  
Alejandro Zentella-Dehesa ◽  
Jesus J. Baquera-Heredia ◽  
...  
Keyword(s):  
Balloon Angioplasty ◽  
Intimal Hyperplasia ◽  
Rabbit Model ◽  
Preliminary Study

scholarly journals Therapeutic modulation of RNA-binding protein Rbm38 facilitates re-endothelialization after arterial injury

2019 ◽  
Vol 115 (12) ◽  
pp. 1804-1810 ◽  
Author(s):  
Kristina Sonnenschein ◽  
Jan Fiedler ◽  
Angelika Pfanne ◽  
Annette Just ◽  
Saskia Mitzka ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Balloon Angioplasty ◽  
Carotid Arteries ◽  
Rna Binding ◽  
Luciferase Reporter ◽  
Binding Motif ◽  
Cell Functions ◽  
Endothelial Regeneration

Abstract Aims Delayed re-endothelialization after balloon angioplasty in patients with coronary or peripheral artery disease impairs vascular healing and leads to neointimal proliferation. In the present study, we examined the effect of RNA-binding motif protein 38 (Rbm38) during re-endothelialization in a murine model of experimental vascular injury. Methods and results Left common carotid arteries of C57BL/6 mice were electrically denudated and endothelial regeneration was evaluated. Profiling of RNA-binding proteins revealed dysregulated expression of Rbm38 in the denudated and regenerated areas. We next tested the importance of Rbm38 in human umbilical vein endothelial cells (HUVECS) and analysed its effects on cellular proliferation, migration and apoptosis. Rbm38 silencing in vitro demonstrated important beneficial functional effects on migratory capacity and proliferation of endothelial cells. In vivo, local silencing of Rbm38 also improved re-endothelialization of denuded carotid arteries. Luciferase reporter assay identified miR-98 and let-7f to regulate Rbm38 and the positive proliferative properties of Rbm38 silencing in vitro and in vivo were mimicked by therapeutic overexpression of these miRNAs. Conclusion The present data identified Rbm38 as an important factor of the regulation of various endothelial cell functions. Local inhibition of Rbm38 as well as overexpression of the upstream regulators miR-98 and let-7f improved endothelial regeneration in vivo and thus may be a novel therapeutic entry point to avoid endothelial damage after balloon angioplasty.

scholarly journals E-Selectin Blockade Decreases Adventitial Inflammation and Attenuates Intimal Hyperplasia in Rat Carotid Arteries After Balloon Injury

2004 ◽  
Vol 24 (11) ◽  
pp. 2063-2068 ◽  
Author(s):  
Ryo Gotoh ◽  
Jun-ichi Suzuki ◽  
Hisanori Kosuge ◽  
Tsunekazu Kakuta ◽  
Shinji Sakamoto ◽  
...  
Keyword(s):  
Intimal Hyperplasia ◽  
Carotid Arteries ◽  
Balloon Injury

Ultimate Strength of the Adventitia and Media of Human Atherosclerotic Carotid Arteries in the Axial and Circumferential Directions

2009 ◽  
Author(s):  
Zhongzhao Teng ◽  
Allen H. Hoffman ◽  
Jie Zheng ◽  
Pamela K. Woodard ◽  
Dalin Tang
Keyword(s):  
Experimental Data ◽  
Mechanical Properties ◽  
Atherosclerotic Plaque ◽  
Balloon Angioplasty ◽  
Cardiovascular Events ◽  
Computational Models ◽  
Carotid Arteries ◽  
Material Strength ◽  
Rupture Mechanism ◽  
Insight Into

The abrupt closure of an artery by an occlusive thrombus is the main cause of myocardial infarcts and other thrombotic sequelae of atherosclerosis. This thrombosis is often associated with rupture of an atherosclerotic plaque [1,2]. Histology has shown that most rupture sites are also sites of increased mechanical stress [2]. It has been widely accepted that atherosclerosis leads to locally increased stresses in the region of lesions. However, validation of this hypothesis has been impeded by a lack of experimental data on the material strength of atherosclerotic tissues. Knowledge of mechanical properties of human atherosclerotic tissues is essential for understanding the rupture mechanism and also for creating more accurate computational models for predicting fatal cardiovascular events [3]. Moreover, an increased understanding of the mechanical properties of atherosclerotic tissue is important for developing greater insight into the pathophysiology of the cardiovascular system and as well as for predicting the outcome of interventional treatments such as balloon angioplasty.

Sign in / Sign up

Export Citation Format

Share Document