Molecular Mechanism of (−)-Epigallocatechin-3-gallate on Balloon Injury-Induced Neointimal Formation and Leptin Expression

2014 ◽  
Vol 62 (6) ◽  
pp. 1213-1220 ◽  
Author(s):  
Chiu-Mei Lin ◽  
Sheng-Wen Hou ◽  
Bao-Wei Wang ◽  
Jiann-Ruey Ong ◽  
Hang Chang ◽  
...  
2010 ◽  
Vol 104 (3) ◽  
pp. 326-335 ◽  
Author(s):  
Ming-Jyh Sheu ◽  
Hsu-Chen Cheng ◽  
Yi-Chung Chien ◽  
Pei-Yu Chou ◽  
Guang-Jhong Huang ◽  
...  

The pathological mechanism of restenosis is primarily attributed to excessive proliferation of vascular smooth muscle cells (VSMC). The preventive effects of ethanol extract of Dunaliella salina (EDS) on balloon injury-induced neointimal formation were investigated. To explore its molecular mechanism in regulating cell proliferation, we first showed that EDS markedly reduced the human aortic smooth muscle cell proliferation via the inhibition of 5′-bromo-2′-deoxyuridine (BrdU) incorporation at 40 and 80 μg/ml. This was further supported by the G0/G1-phase arrest using a flow cytometric analysis. In an in vivo study, EDS at 40 and 80 μg/ml was previously administered to the Sprague–Dawley rats and found that the thickness of neointima, and the ratio of neointima:media were also reduced. EDS inhibited VSMC proliferation in a dose-dependent manner following stimulation of VSMC cultures with 15 % fetal bovine serum (FBS). Suppressed by EDS were 15 % FBS-stimulated intracellular Raf, phosphorylated extracellular signal-regulated kinases (p-Erk) involved in cell-cycle arrest and proliferating cell nuclear antigen. Phosphorylated focal adhesion kinase (p-FAK) was also suppressed by EDS. Also active caspase-9, caspase-3 and cleaved poly(ADP-ribose) polymerase (PARP) protein expression levels were increased by administration with EDS; the apoptotic pathway may play an important role in the regulatory effects of EDS on cell growth. These observations provide a mechanism of EDS in attenuating cell proliferation, thus as a potential intervention for restenosis.


2013 ◽  
Vol 109 (11) ◽  
pp. 2113-2113
Author(s):  
Ming-Jyh Sheu ◽  
Hsu-Chen Cheng ◽  
Yi-Chung Chien ◽  
Pei-Yu Chou ◽  
Guang-Jhong Huang ◽  
...  

2018 ◽  
Vol 234 (7) ◽  
pp. 11545-11554
Author(s):  
Yang He ◽  
Bei Sun ◽  
Gang Chen ◽  
Renping Huang

2020 ◽  
Vol 25 (6) ◽  
pp. 570-577
Author(s):  
Nikolaos P. E. Kadoglou ◽  
Marianna Stasinopoulou ◽  
Triantafyllos Giannakopoulos ◽  
Anastasios Papapetrou ◽  
Constantinos Dimitriou ◽  
...  

Background: The purpose of the study was the comparative assessment of ticagrelor and clopidogrel effects on carotid post-balloon injury (PBI) and on post carotid artery stenting (CAS) rate of in-stent restenosis (ISR) and in-stent thrombosis in atherosclerotic rabbits. Methods: Forty-eight New Zealand white rabbits on high-fat diet were randomized into 4 groups: A1: PBI and clopidogrel (30 mg/kg/d), A2: PBI and ticagrelor (21 mg/kg twice daily), B1: PBI, CAS, and clopidogrel (30 mg/kg/d), B2: PBI, CAS, and ticagrelor (21 mg/kg twice daily). All rabbits received orally aspirin (10 mg/kg/d) and interventions were performed in their right carotid arteries (RCAs). Optical coherence tomography (OCT) and carotid angiography were performed at end point, while platelet aggregation and lipid profile were measured. After euthanasia both carotids were obtained for histological examination. Results: In B1 group, 3 rabbits presented thrombotic total occlusion of the stents, while none such episode was observed in B2 group. The neointimal areas in RCAs, calculated by OCT, did not differ between A1 and A2 groups, and between B1 and B2 groups ( P > .05). From the histological findings, the intima/(media + intima) percentage (%) in RCAs of balloon-injured rabbits did not present any difference between groups ( P = .812). Similarly, the immunohistochemically determined accumulation of endothelial cells and macrophages on vascular walls was equivalent between groups ( P > .05). Conclusion: Following carotid balloon injury and stenting, clopidogrel and ticagrelor did not show any differential effects on the extent of neointimal formation and ISR in atherosclerotic rabbits receiving aspirin. Three thrombotic stent occlusions were noted in the clopidogrel treatment group, but this finding was not statistically significant.


2009 ◽  
Vol 296 (5) ◽  
pp. H1532-H1539 ◽  
Author(s):  
Bradley S. Fleenor ◽  
Douglas K. Bowles

Adventitial fibroblasts have previously been proposed to be a major constituent of the neointima following coronary balloon angioplasty. The present study utilized the bromodeoxyuridine (BrdU) pulse-chase technique to track adventitial fibroblast migration early after balloon injury in swine. BrdU (30 mg/kg), a marker of proliferating cells, was given intravenously 1 or 2 days after balloon angioplasty. For each time point, one animal was euthanized 24 h after injection to identify the location of the proliferating cells, while a second animal was euthanized 25 days after angioplasty to determine whether the proliferating cells migrated to form the neointima. Our results demonstrate that BrdU-positive cells were located primarily in the adventitia with all three time points 24 h after balloon angioplasty. Furthermore, when BrdU was injected on day 1 or 2 only 0.65 ± 0.17% and 1.7 ± 0.64%, respectively, of neointimal cells were BrdU positive on day 25. In conclusion, these results demonstrate a negligible contribution of coronary adventitial fibroblasts to neointima formation following coronary balloon angioplasty, supporting the concept that the neointima is primarily of smooth muscle cell origin.


2012 ◽  
Vol 11 (1) ◽  
pp. 150 ◽  
Author(s):  
Jingsheng Guo ◽  
Dongye Li ◽  
Shiru Bai ◽  
Tongda Xu ◽  
Zhongmin Zhou ◽  
...  

2004 ◽  
Vol 22 (Suppl. 1) ◽  
pp. S87 ◽  
Author(s):  
K Yamasaki ◽  
N Tomita ◽  
Y Kunugiza ◽  
H Koike ◽  
M Aoki ◽  
...  

2010 ◽  
Vol 336 (2) ◽  
pp. 533-539 ◽  
Author(s):  
Kento Kitada ◽  
Nozomi Yui ◽  
Maki Koyama ◽  
Kimihiro Kimura ◽  
Rie Suzuki ◽  
...  

2006 ◽  
Vol 290 (1) ◽  
pp. E92-E102 ◽  
Author(s):  
Hong Pei ◽  
Jiali Gu ◽  
Pushpa-Rekha Thimmalapura ◽  
Angeles Mison ◽  
Jerry L. Nadler

Insulin resistance (IR) is associated with an increased risk of cardiovascular diseases. The obese Zucker rat (ZR) is a model of IR that shows markedly increased insulin and triglyceride concentrations without major changes in glucose. In this study, we evaluated the response of obese and lean ZR to carotid balloon injury and determined potential mechanisms and treatments. The neointima-to-media ratio of obese ZR was greater than that of lean ZR, starting at 14 days after injury, and persisted until at least day 30. An enhanced inflammatory response to balloon injury in the obese ZR was reflected by significantly higher ED1-positive macrophage cells in the injured vessel wall compared with that in lean ZR at 3, 7, and 14 days after balloon injury. Inflammatory mediators 12-lipoxygenase (12-LO) and STAT4 were studied in neointimal lesions. Expression of 12-LO RNA was increased beginning at day 7 and showed increases of 4.3-fold on day 14 and 7-fold on day 30 in obese ZR compared with lean animals. Staining of phosphorylated STAT4 (PSTAT4), the activated form of STAT4, in lesions from obese ZR was also increased compared with that in leans. We tested the effects of a novel anti-inflammatory agent, lisofylline (LSF), in the obese ZR. LSF markedly reduced neointimal formation in the obese ZR. LSF also reduced monocyte/macrophage infiltration into the vessel wall and the activation of PSTAT4. These studies suggest both the presence of an exaggerated injury response in the insulin-resistant obese ZR model and that inflammation plays a major role in mediating neointimal growth.


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