Negligible contribution of coronary adventitial fibroblasts to neointimal formation following balloon angioplasty in swine

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.

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Characterization and Functions of Vascular Adventitial Fibroblast Subpopulations

Cellular Physiology and Biochemistry ◽

10.1159/000373939 ◽

2015 ◽

Vol 35 (3) ◽

pp. 1137-1150 ◽

Cited By ~ 11

Author(s):

Sheng Jun An ◽

Pei Liu ◽

Tie Mei Shao ◽

Zhi Jun Wang ◽

Hai Gang Lu ◽

...

Keyword(s):

Cardiovascular Diseases ◽

Receptor Antagonist ◽

Vascular Remodeling ◽

Collagen Type ◽

Collagen Type I ◽

Type I ◽

Ang Ii ◽

Neointimal Formation ◽

Adventitial Fibroblasts ◽

Adventitial Fibroblast

Background: Adventitial fibroblasts have been shown to play an important role in vascular remodeling and contribute to neointimal formation in vascular diseases. However, little is known about adventitial fibroblast subpopulations. This study explored the process of isolating rat thoracic aorta adventitial fibroblast subpopulations and characterized their properties following stimulation with angiotensin II (ANG II), a critical factor involved in cardiovascular diseases such as hypertension. Methods: Adventitial fibroblasts were isolated and cultured from rat aorta. Fibroblast subpopulations were individually expanded using cloning ring techniques. Cells were treated with ANG II (10 nM, 100 nM and 1 μM) for 0.5, 1, 1.5, 3, 6, 12, or 24 h, and ANG II-induced proliferation and migration were measured by MTT assay and Transwell. Cells were treated with ANG II (100 nM) in the presence or absence of ANG II receptor antagonists (100 μM), losartan (for AT1) and PD-123319 (for AT2). PreproET-1 mRNA and ET-1 were determined by RT-PCR and ELISA, respectively. Collagen type I was detected by western blotting. Results: Two major fibroblast subpopulations were found in the adventitia, epithelioid-like cells and spindle-like cells; Although ANG II promotes the growth of both subpopulations, epithelioid-like cell proliferation shows dose-dependency on ANG II from 10 nM to 1 μM, while proliferation of spindle-like cells reaches a peak value following 100 nM ANG II stimulation; ANG II stimulation enhanced epithelioid-like but not spindle-like cell migration; ANG II dose-dependently increased the expression of preproET-1 and collagen type I, and enhanced ET-1 secretion in epithelioid-like but not spindle-like cells, effects abolished by the AT1 receptor antagonist, but not with AT2 receptor antagonist. Conclusion: Adventitial fibroblasts are heterogeneous and epithelioid-like subpopulations with high sensitivity to ANG II stimulation may be implicated in the pathophysiological mechanisms of vascular remodeling, reparative processes and cardiovascular diseases.

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Dihydroartemisinin ameliorates balloon injury‐induced neointimal formation in rats

Journal of Cellular Physiology ◽

10.1002/jcp.27809 ◽

2018 ◽

Vol 234 (7) ◽

pp. 11545-11554

Author(s):

Yang He ◽

Bei Sun ◽

Gang Chen ◽

Renping Huang

Keyword(s):

Balloon Injury ◽

Neointimal Formation

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Egr-1 antisense oligonucleotides inhibit hypoxia-induced proliferation of pulmonary artery adventitial fibroblasts

Journal of Applied Physiology ◽

10.1152/japplphysiol.00821.2004 ◽

2005 ◽

Vol 98 (2) ◽

pp. 732-738 ◽

Cited By ~ 37

Author(s):

Mark F. Banks ◽

Evgenia V. Gerasimovskaya ◽

Doug A. Tucker ◽

Maria G. Frid ◽

Todd C. Carpenter ◽

...

Keyword(s):

Cell Proliferation ◽

Pulmonary Artery ◽

Antisense Oligonucleotides ◽

Mammalian Species ◽

Growth Factor Receptor ◽

Immunohistochemical Analysis ◽

Fibroblast Proliferation ◽

Adventitial Fibroblasts ◽

Adventitial Fibroblast

In most mammalian species, chronic exposure to hypoxia leads to pulmonary hypertension and vascular remodeling. The adventitial fibroblast, because of its ability to proliferate in response to hypoxia, is thought to be a critical cell in the remodeling process. However, the transcription factors driving hypoxia-induced fibroblast proliferation have yet to be elucidated. The early growth response-1 (Egr-1) transcription factor has been shown to be upregulated by hypoxia in pulmonary artery adventitial fibroblasts. We therefore hypothesized that Egr-1 is directly involved in hypoxia-induced adventitial fibroblast proliferation. Immunohistochemical analysis of in vivo lung tissue from animals exposed to chronic hypoxia revealed increased expression of Egr-1 in the pulmonary artery fibroblasts vs. expression shown in normoxic controls. In fibroblasts cultured from chronically hypoxic animals, exposure to 1% oxygen upregulated Egr-1 protein and cell proliferation. To evaluate the role of Egr-1 in hypoxia-induced proliferation, we employed an Egr-1 antisense strategy. Addition of antisense Egr-1 oligonucleotides, but not sense oligonucleotides, attenuated the hypoxia-induced upregulation of Egr-1 protein and reduced hypoxia-induced DNA synthesis by 50%. Cell proliferation was also significantly inhibited by the addition of antisense Egr-1 oligonucleotides but not the sense oligonucleotides. In addition, hypoxia-induced upregulations of cyclin D and epidermal growth factor receptor were attenuated by Egr-1 antisense oligonucleotides. We conclude that Egr-1 protein expression is very sensitive to upregulation by hypoxia in pulmonary artery adventitial fibroblasts and that it plays an important role in the autonomous growth phenotype induced by hypoxia in these cells.

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Carotid Stent Restenosis and Thrombosis in Rabbits: The Effect of Antiplatelet Agents

Journal of Cardiovascular Pharmacology and Therapeutics ◽

10.1177/1074248420931624 ◽

2020 ◽

Vol 25 (6) ◽

pp. 570-577

Author(s):

Nikolaos P. E. Kadoglou ◽

Marianna Stasinopoulou ◽

Triantafyllos Giannakopoulos ◽

Anastasios Papapetrou ◽

Constantinos Dimitriou ◽

...

Keyword(s):

High Fat Diet ◽

Carotid Arteries ◽

Antiplatelet Agents ◽

Balloon Injury ◽

Neointimal Formation ◽

Total Occlusion ◽

Stent Restenosis ◽

Vascular Walls ◽

New Zealand White Rabbits ◽

Group 3

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.

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Fibroblast Growth Factor Receptor-1 Signaling Induces Osteopontin Expression and Vascular Smooth Muscle Cell–Dependent Adventitial Fibroblast Migration In Vitro

Circulation ◽

10.1161/01.cir.0000024113.26985.cc ◽

2002 ◽

Vol 106 (7) ◽

pp. 854-859 ◽

Cited By ~ 43

Author(s):

Guohong Li ◽

Suzanne Oparil ◽

Stacey S. Kelpke ◽

Yiu-Fai Chen ◽

John A. Thompson

Keyword(s):

Smooth Muscle ◽

Growth Factor ◽

Fibroblast Growth Factor ◽

Fibroblast Growth Factor Receptor ◽

Growth Factor Receptor ◽

Fibroblast Growth ◽

Fibroblast Migration ◽

Osteopontin Expression ◽

Adventitial Fibroblast

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Detecting DNA synthesis of neointimal formation after catheter balloon injury in GK and in Wistar rats: using 5-ethynyl-2'-deoxyuridine

Cardiovascular Diabetology ◽

10.1186/1475-2840-11-150 ◽

2012 ◽

Vol 11 (1) ◽

pp. 150 ◽

Cited By ~ 10

Author(s):

Jingsheng Guo ◽

Dongye Li ◽

Shiru Bai ◽

Tongda Xu ◽

Zhongmin Zhou ◽

...

Keyword(s):

Dna Synthesis ◽

Wistar Rats ◽

Balloon Injury ◽

Neointimal Formation

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

Journal of Agricultural and Food Chemistry ◽

10.1021/jf404479x ◽

2014 ◽

Vol 62 (6) ◽

pp. 1213-1220 ◽

Cited By ~ 7

Author(s):

Chiu-Mei Lin ◽

Sheng-Wen Hou ◽

Bao-Wei Wang ◽

Jiann-Ruey Ong ◽

Hang Chang ◽

...

Keyword(s):

Molecular Mechanism ◽

Balloon Injury ◽

Neointimal Formation ◽

Leptin Expression

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INHIBITION OF NEOINTIMAL FORMATION BY BERAPROST SODIUM (BPS) IN THE PORCINE CORONARY ARTERY AFTER BALLOON INJURY

Journal of Hypertension ◽

10.1097/00004872-200402001-00371 ◽

2004 ◽

Vol 22 (Suppl. 1) ◽

pp. S87 ◽

Cited By ~ 1

Author(s):

K Yamasaki ◽

N Tomita ◽

Y Kunugiza ◽

H Koike ◽

M Aoki ◽

...

Keyword(s):

Coronary Artery ◽

Balloon Injury ◽

Neointimal Formation ◽

Porcine Coronary Artery ◽

Beraprost Sodium

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BMSCs Interactions with Adventitial Fibroblasts Display Smooth Muscle Cell Lineage Potential in Differentiation and Migration That Contributes to Neointimal Formation

Stem Cells International ◽

10.1155/2016/3196071 ◽

2016 ◽

Vol 2016 ◽

pp. 1-10 ◽

Cited By ~ 4

Author(s):

Y. Wendan ◽

J. Changzhu ◽

S. Xuhong ◽

C. Hongjing ◽

S. Hong ◽

...

Keyword(s):

Smooth Muscle ◽

Cell Lineage ◽

Immunofluorescence Staining ◽

Neointimal Formation ◽

Migration Ability ◽

Reverse Transcription Pcr ◽

Adventitial Fibroblasts ◽

And Migration

In this study a model of simulated vascular injury in vitro was used to study the characterization of bone-marrow-derived mesenchymal stem cells (BMSCs) morphology and to investigate the differentiation and migration of BMSCs in the presence of adventitial fibroblasts. BMSCs from rats were indirectly cocultured with adventitial fibroblasts in a transwell chamber apparatus for 7 days, and clonogenic assays demonstrated that BMSCs could be differentiated into smooth muscle-like cells with this process, including smooth muscleα-actin (α-SMA) expression by immunofluorescence staining. Cell morphology of BMSCs was assessed by inverted microscope, while cell proliferation was assessed by MTT assay. The expressions of TGF-β1, MMP-1, and NF-κB were detected by immunofluorescence staining and Smad3 mRNA was measured by reverse transcription PCR. Migration ability of BMSCs with DAPI-labeled nuclei was measured by laser confocal microscopy. Our results demonstrate that indirect interactions with adventitial fibroblasts can induce proliferation, differentiation, and migration of BMSCs that can actively participate in neointimal formation. Our results indicate that the pathogenesis of vascular remodeling might perform via TGF-β1/Smad3 signal transduction pathways.

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