Trichosanthin attenuates vascular injury-induced neointimal hyperplasia following balloon catheter injury in rats

Neointimal hyperplasia is the major cause of carotid stenosis after vascular injury, which restricts the long-term efficacy of endovascular treatment and endarterectomy in preventing stenosis. Ginsenoside Re (Re) is a...

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Balloon catheter injury abolishes phenylephrine-induced relaxation in the rat contralateral carotid

British Journal of Pharmacology ◽

10.1111/j.1476-5381.2011.01275.x ◽

2011 ◽

Vol 163 (4) ◽

pp. 770-781 ◽

Cited By ~ 11

Author(s):

L Pernomian ◽

MS Gomes ◽

AM de Oliveira

Keyword(s):

Balloon Catheter ◽

Balloon Catheter Injury

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Differential Effects of Peroxisome Proliferator Activator Receptor-α and γ Ligands on Intimal Hyperplasia After Balloon Catheter-Induced Vascular Injury in Zucker Rats

Journal of Cardiovascular Pharmacology and Therapeutics ◽

10.1177/107424840300800407 ◽

2003 ◽

Vol 8 (4) ◽

pp. 297-305 ◽

Cited By ~ 31

Author(s):

Cyrus V. Desouza ◽

S. N. Murthy ◽

Jose Diez ◽

Bruce Dunne ◽

Anil S. Matta ◽

...

Keyword(s):

Vascular Injury ◽

Intimal Hyperplasia ◽

Balloon Catheter ◽

Zucker Rats ◽

Peroxisome Proliferator ◽

Differential Effects

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Neointimal hyperplasia regression using combined paclitaxel- mediated confocal dual pulse shock wave sonoporation therapy and catheter- based 90Y- mediated brachytherapy

European Heart Journal ◽

10.1093/eurheartj/ehab724.2003 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

H Mehrad

Keyword(s):

Shock Wave ◽

Smooth Muscle ◽

Treatment Group ◽

Neointimal Hyperplasia ◽

Balloon Catheter ◽

Public Institution ◽

Cavitation Effect ◽

Muscle Hyperplasia ◽

Smooth Muscle Hyperplasia ◽

Tunica Intima

Abstract Background and aims Intimal hyperplasia refers to proliferation and migration of vascular smooth muscle cells primarily in the tunica intima, resulting in arterial wall thickening and decreased arterial lumen size. Neointimal hyperplasia is the major cause of restenosis after percutaneous carotid interventions such as stenting or angioplasty. The aim of this study was to investigate the effect of combined shock wave enhanced sonoporation therapy and catheter-based 90Y-mediated β-brachytherapy on neointimal hyperplasia regression in an animal model, wherein diagnostic B-mode ultrasound is combined with therapy system, with a goal of increased safety. Methods Endothelial balloon catheter denudation of the abdominal aorta of golden Syrian hamsters was performed. Histopathologic evaluation confirmed neointimal hyperplasia formation in all of the hamsters' arteries. The treatment group underwent intravenous lipid-based encapsulated paclitaxel nanoparticles (10mg/kg)-mediated extracorporeal confocal dual pulse low-level focused electrohydraulic shock wave (V=15 kV, F=2 Hz, Impulses = 50 and V=10 kV, F=0.2 Hz, Impulses = 150) enhanced sonoporation therapy accompanied by catheter-based 90Y-mediated β-brachytherapy (90Y, 15 Gy), guided by simultaneous B-mode ultrasound imaging. Results B-mode ultrasound guided combined shock wave enhanced sonoporation therapy and β-brachytherapy was feasible and appeared safe for the targeting of stenosis in the aorta artery. Furthermore, pathological results showed a significant reduction in the mean value for smooth muscle hyperplasia cells density, lumen wall thickness and percentage of luminal cross- sectional area of stenosis in the treatment group compared with the other groups (p<0.05). Conclusions Enhanced toxicity effect of paclitaxel, induced by enhanced sonoporation effect of shock wave therapy, due to inertial cavitation effect of collapsed capsules and dual pulse system application accompanied by apoptotic effect of brachytherapy, can cause to neointimal hyperplasia regression. Combined shock wave enhanced sonoporation therapy and β-brachytherapy is significantly associated with reduced aorta artery stenosis in hamsters. The mechanism may relate to reduced smooth muscle hyperplasia cells and inflammation in the tunica intima. FUNDunding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Mehrad Research Lab

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Abstract 5494: ADAMTS-7 is Critical for Vascular Smooth Muscle Cell Migration and Neointima Formation in Injured Rat Carotid Artery

Circulation ◽

10.1161/circ.118.suppl_18.s_560-d ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Wei Kong ◽

Li Wang ◽

Xue Bai ◽

Bo Liu ◽

Yi Zhu ◽

...

Keyword(s):

Smooth Muscle ◽

Vascular Smooth Muscle ◽

Vascular Injury ◽

Matrix Protein ◽

Mrna Level ◽

Balloon Catheter ◽

Migration And Invasion ◽

Neointima Formation ◽

Subsequent Increase ◽

Neointimal Thickening

Migration of vascular smooth muscle cells (VSMCs) plays an essential role during vascular development, in response to vascular injury and during atherogenesis. Extensive studies have implicated the importance of extracellular matrix (ECM)-degrading proteinases during VSMCs migration. ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs), a recently described family of proteinases, is capable of degrading vascular ECM proteins. However, the relevance of ADAMTS family members in cardiovascular disease is poorly understood. In this study, we sought to determine whether ADAMTS-7 is involved in VSMC migration and neointima formation in response to vascular injury. Denudation of rat carotid arteries with a balloon catheter led to an initial decrease of ADAMTS-7 protein level in injured compared with sham-operated arteries within the first 24 hours, followed by a subsequent increase during the 4 to 14 days after injury. In primary VSMCs, the pro-inflammatory cytokine TNF-α increased ADAMTS-7 mRNA level through transcriptional factors nuclear factor-kappa B and AP-1. VSMCs infected with ADAMTS-7 adenovirus (Ad-ADAMTS-7) greatly accelerated their migration and invasion in vitro . Conversely, suppression of ADAMTS-7 expression by small interfering RNA (siRNA) markedly retarded VSMC movement by 50% than that with scramble siRNA. At 7 days after injury, the neointimal area of the vascular wall was sixfold greater in Ad-ADAMTS-7-infected than that in Ad-GFP-infected vessels (3.10±0.88 vs. 0.52±0.28 ×10 4 μm 2 , n=8 per group, P <0.05). By contrast, perivascular administration of ADAMTS-7 siRNA, but not scramble siRNA to injured arteries resulted in prolonged ADAMTS-7 silencing and diminished neointimal thickening without affecting medial areas. This inhibitory effect was sustained up to 14 days after injury. As well, ADAMTS-7 mediated degradation of the vascular ECM cartilage oligomeric matrix protein (COMP) in injured vessels, which might facilitate VSMC migration and neointimal thickening. ADAMTS-7 directs VSMC migration and neointima formation and therefore may serve as a novel therapeutic target for vascular restenosis and atherogenesis.

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Abstract 286: The Role of Gut Microbiota in Neointimal Hyperplasia After Vascular Injury

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.35.suppl_1.286 ◽

2015 ◽

Vol 35 (suppl_1) ◽

Author(s):

Karen J Ho ◽

Liqun Xiong ◽

Nathaniel Hubert ◽

Anuradha Nadimpalli ◽

Eugene B Chang ◽

...

Keyword(s):

Cell Cycle ◽

Vascular Injury ◽

Sodium Butyrate ◽

Gut Microbiome ◽

Neointimal Hyperplasia ◽

Cell Counting ◽

Rrna Gene ◽

Control Analysis ◽

Dependent Manner ◽

Microbial Composition

Introduction: There is increasing evidence that the gut microbiome regulates susceptibility to certain diseases through systemic effects of microbe-derived metabolites. Sodium butyrate is a short chain fatty acid that is produced by microbial fermentation of dietary fiber and has known anti-proliferative and anti-migratory effects on vascular smooth muscle cells (VSMC). We hypothesized that perturbation of the gut microbiome with antibiotics would alter systemic serum butyrate concentration and impact neointimal hyperplasia after vascular injury. Methods: 10-wk-old male Lewis Inbred rats were treated with vancomycin (“vanco”) in the drinking water (0.5mg/mL) ± sodium butyrate (“buty”, 0.5mg/mL) for 4 wks prior to undergoing left carotid angioplasty. Serum butyrate concentration was assessed by gas chromatography. Gut microbial composition was assessed by 16S rRNA gene surveys of fecal samples. VSMC were treated with butyrate (0-5mM) and assessed for cell proliferation using cell counting, cell migration using a transwell assay, and cell cycle progression using FACS. Results: Post-angioplasty carotid arteries from vanco-treated rats developed 38% more neointima than controls (0.032±0.004mm2 vs. 0.044±0.003 mm2, P=0.02), but vanco+buty treatment prevented this increase in intimal area (0.035±0.004 mm2, P=.62 vs. control). Analysis of gut microbial communities revealed unique shifts in bacterial clustering by treatment group, which correlated with changes in serum butyrate levels, with the lowest butyrate level detected in vanco-treated rats (0.54±0.1 μmol/mL control, 0.017±0.1 μmol/mL vanco, 0.45±0.1 μmol/mL vanco+buty, P=.008). In vitro, butyrate treatment inhibited VSMC proliferation at 24-48 hrs in a dose-dependent manner, which correlated with induction of G0/G1 cell cycle arrest (P=.001) and a reduction in chemotaxis (P=.03). Conclusions: Oral vancomycin treatment induced a shift in the gut microbial community that was associated with decreased serum butyrate levels and increased neointimal hyperplasia, both of which were reversed by oral butyrate supplementation. These data demonstrate proof-of-concept that there is a correlation between gut microbial dysbiosis and susceptibility to neointimal hyperplasia.

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Abstract 1126: Adiponectin Prevents Neointimal Hyperplasia After Vascular Injury In Adiponectin Transgenic Mice

Circulation ◽

10.1161/circ.116.suppl_16.ii_226-d ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

yasutoshi omori

Keyword(s):

Endothelial Cells ◽

Smooth Muscle ◽

Transgenic Mice ◽

Vascular Injury ◽

Tissue Concentration ◽

Adiponectin Level ◽

Neointimal Hyperplasia ◽

Intercellular Adhesion Molecule ◽

Morphometrical Analysis ◽

Anti Body

Background: Adiponectin has been reported to accumulate in the human injured artery and regulate the development of atherosclerosis, decreasing the expression of adhesion molecules in vascular endothelial cells, and inhibiting the proliferation of vascular smooth muscle cells. However, the role of adiponection after vascular injury is not fully elucidated. Therefore, we investigate whether adiponectin prevents neointimal hyperplasia after vascular injury in adiponectin transgenic mice (TG). Methods: C57/BL6 mice (WT) and TG of 6 –7 week age were used. We inserted a large wire (0.38 mm in diameter) into femoral artery from distal side to proximal side to make the vascular endothelium damaged model. Mice were sacrificed at 1, 2 and 4 weeks, and non injured mice were used as control. Tissue concentration of fat and liver and serum concentration of adiponectin was measured using ELISA. Intima/ media ratio was measured in morphometrical analysis. Immunohistochemical staining of anti-adiponectin, anti-α-smooth muscle embryo (α-SMemb), anti-α-smooth muscle cell actin, von Willebrand Factor (vWF) and intercellular adhesion molecule-1 (ICAM-1) was performed using paraffin embedded sections. Result: In immunohistochemical analysis at 1 week, α-SMemb positive cells, which were also positive for ICAM-1 were observed in WT, but were not seen in TG. Adiponectin positive cells, which were also positive for vWF were observed in the endothelial cells in TG, but were not detected in WT at 1 week, but those cells were observed in th endothelial cells in TG and WT at 2 and 4 weeks. In α-SMA staining at 4 weeks most neointimal area was stained with this anti-body in TG. On the other hand, in neointima of WT, only some area was stained with this anti-body. In morphometrical analysis, intima/media ratio was significantly smaller in TG than in WT at 1, 2 and 4 weeks. Adiponectin concentration of fat, liver and serum was significantly higher in TG than in WT in non-injured model and at 4 weeks. At 1 week liver and fat adiponectin level is significantly higher in TG than in WT, and serum adiponectin level in TG tended to be high as compared to that of WT. Conclusions: Adiponectin prevents neointimal hyperplasia after vascular injury, probably through the inhibition of inflammatory reaction.

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