In Vivo Effect of TGF-β1

Kanzaki, Tetsuto; Tamura, Ken; Takahashi, Kazuo; Saitō, Yasushi; Akikusa, Bunshiro; Oohashi, Hideya; Kasayuki, Noriaki; Ueda, Makiko; Morisaki, Naho

doi:10.1161/01.atv.15.11.1951

Cited by 109 publications

(48 citation statements)

References 41 publications

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“…21 The latter is similar to the manner in which cell growth is inhibited by shear stress. 22 Although in vivo studies have demonstrated that overexpression of TGF-␤1 by direct transfer of TGF-␤1 gene into porcine arteries 23 or systemic administration of TGF-␤1 after balloon injury in rabbits 24 induces extracellular matrix (ECM) synthesis and deposition in arterial wall, the role of flow and related shear-mediated forces in modulating wild-type TGF-␤1 in the arterial wall has not been investigated. In the present study, we determined TGF-␤1 mRNA and protein levels in the injured New Zealand White male rabbit carotid arteries in relation to varying flow and wall shear conditions at 3, 7, and 14 days.…”

mentioning

confidence: 99%

Increased Flow and Shear Stress Enhance In Vivo Transforming Growth Factor-β1 After Experimental Arterial Injury

Song

Kocharyan

Fortunato

et al. 2000

ATVB

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Abstract-We have previously demonstrated that high-flow (HF) conditions inhibit experimental intimal hyperplasia.We hypothesized that such flow conditions may alter transforming growth factor-␤1 (TGF-␤1) after mural injury. The right common carotid artery (CCA) was balloon-injured in 54 New Zealand White male rabbits. Flow was thereafter preserved (normal flow [NF]), reduced by partial outflow occlusion (low flow [LF]), or increased by ligation of the left CCA (HF). Four sham-operated animals served as uninjured controls. Mean blood flow and pressure in the right CCA were measured before and after flow modulation and before euthanasia (3, 7, and 14 days). TGF-␤1 mRNA and protein levels in the right CCA were determined by Northern and ELISA analyses at each time point. At 7 and 14 days, intimal hyperplasia was quantified, and the transmural localization of TGF-␤1 was determined by immunohistochemical analysis. Mean flow was reduced from 22Ϯ1 to 10Ϯ3 mL/min in the LF group and increased to 34Ϯ2 mL/min in the HF group (PϽ0.001). Blood pressure was not different among the flow groups for all time points. Wall shear stress was markedly decreased in the LF group to 14Ϯ4 dyne/cm 2 and increased in the HF group to 63Ϯ6 dyne/cm 2 at 7 days compared with values in uninjured controls (39Ϯ2 dyne/cm 2 , PϽ0.001) and the NF group (44Ϯ7 dyne/cm 2 , PϽ0.001). At 14 days, wall shear stress was similar among the flow groups. The intima-to-media ratio was 5-and 2-fold greater in the LF group than in the HF and NF groups at 14 days. mRNA levels for TGF-␤1 and its active ligand were increased in the HF group by at least 2-and 3-fold, respectively, at 3 and 7 days compared with levels in uninjured controls and the LF group (PϽ0.05) but were not different among the flow groups at 14 days. TGF-␤1 preferentially localized in the abluminal vascular smooth muscle cells of the HF arterial segments. Flow-and shear-mediated release of TGF-␤1 may therefore play a role in abrogating the proliferative and migratory response of vascular smooth muscle cells in the early stages after mural injury.

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mentioning

confidence: 99%

Increased Flow and Shear Stress Enhance In Vivo Transforming Growth Factor-β1 After Experimental Arterial Injury

Song

Kocharyan

Fortunato

et al. 2000

ATVB

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“…6 -18,57-61 In vitro effects on cells in artificial culture conditions represent, by necessity, a simplistic approach to the mechanisms involved. Other hypotheses, which were not studied here, can also be considered, such as the chemotactic actions of GFs on inflammatory cells and vascular smooth muscle cells, 10 -12,60,61 effects on cell differentiation, [62][63][64] thrombogenic properties of TGF-␤ 1 in vivo, 65 or even induction of tissue factor expression. 66 We have shown in earlier studies that neointima formation at the neck of porcine aneurysms could be significantly increased at 2 weeks by the local delivery of PE rich in TGF-␤ 1 and PDGF-BB.…”

Section: Gfs and Neointima Formationmentioning

confidence: 99%

“…The in vivo response to GFs witnessed in our model seems to be nonspecific, and one hypothesis is that exogenous GFs encourage recruitment of inflammatory cells, which are themselves a more persistent source of GFs and cytokines important to healing phenomena, as proposed in other experimental studies. 65,67 …”

Section: Gfs and Neointima Formationmentioning

confidence: 99%

Growth Factors Stimulate Neointimal Cells In Vitro and Increase the Thickness of the Neointima Formed at the Neck of Porcine Aneurysms Treated by Embolization

Desfaits

Raymond

Muizelaar³

2000

Stroke

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Background and Purpose-Growth factors (GFs) may favor the healing of aneurysms treated with endovascular techniques by stimulating neointima formation. Methods-Bilateral carotid aneurysms were constructed with venous pouches in 50 pigs and embolized intraoperatively with collagen sponges with and without GFs (platelet-derived growth factor-BB [PDGF-BB] 0.15 or 1.5 g or transforming growth factor-␤ 1 [TGF-␤ 1 ] 60 or 600 ng) in each animal. DNA synthesis, cell proliferation, and collagen secretion assays were performed to assess the in vitro effects of GFs on neointimal cells harvested from the treated aneurysms. 125 I-PDGF-BB was used to study in vivo GF release from sponges. The thickness of the neointima at the surface of the sponges was measured 2 weeks after surgery. Since porcine aneurysms tend to heal after collagen sponge embolization, this experiment was repeated in dogs, which have shown a propensity for recurrence with the same technique, with 600 ng TGF-␤ 1 or platelet extracts. Results-PDGF-BB stimulated DNA synthesis and cell proliferation, while TGF-␤ 1 strongly increased collagen synthesis of neointimal cells in vitro. Clearance of 125 I-PDGF-BB from the sponges followed a biphasic curve, with 1.5% of exogenous PDGF-BB remaining at 1 week. The local delivery of PDGF-BB (0.15 or 1.5 g) and TGF-␤ 1 (600 ng) significantly increased neointimal thickness at the neck of porcine aneurysms, while 60 ng of TGF-␤ 1 had no demonstrable effect. TGF-␤ 1 (600 ng) or platelet extracts had no influence on canine aneurysms. Conclusions-PDGF-BB

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“…7,8) Arteries exposed to TGF-β1 after injury lead to a stimulatory effect on platelets activation and thrombogenesis, inflammatory cell infiltration, vascular smooth muscle cell migration and proliferation, extracellular matrix protein synthesis and deposition, and transformation of vascular fibroblasts to myofibroblasts, which finally results in eventual luminal narrowing. [9][10][11][12][13][14][15][16][17] On the contrary, attenuating TGF-β1 activity is assuredly efficacious in diminishing intimal hyperplasia and reducing ISR. [18][19][20][21][22][23] It has been confirmed that there are multiple functional genetic polymorphisms in the TGF-β1 gene which are associated with TGF-β1 expression or function.…”

mentioning

confidence: 99%

Role of Gene Polymorphisms/Haplotypes and Plasma Level of TGF-β1 in Susceptibility to In-Stent Restenosis Following Coronary Implantation of Bare Metal Stent in Chinese Han Patients

Chen

Zhang

et al. 2018

Int. Heart J.

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SummaryTransforming growth factor (TGF)-β1 has been implicated in the pathogenesis of restenosis. However, the role of TGF-β1 polymorphisms in development of in-stent restenosis (ISR) after coronary bare metal stent (BMS) implantation in Chinese Han population has not been reported to date. The aim of this study was to explore the association between TGF-β1 gene polymorphisms (-509C/T and 869T/C) and its plasma level in Chinese Han patients with BMS-ISR.We investigated 419 patients after successful coronary stent placement. All patients were reexamined by angiography. Genotyping for the two TGF-β1 gene polymorphisms was performed using polymerase chain reaction-restriction fragment length polymorphism analysis. Plasma TGF-β1 levels were measured by enzymelinked immunosorbent assay.Ninety-two patients (21.96%) developed ISR during the follow-up period. The multivariable analysis adjusted for potential confounders and it revealed that the C allele of TGF-β1 869T/C polymorphism was linked to an increased risk of ISR in both additive (Per each C allele) and dominant (TC+CC versus TT) models with odds ratios (ORs) of 1.88 (95% confidence interval [CI]: 1.21-2.84, P = 0.008) and 2.52 (95% CI: 1.40-4.80, P = 0.005), respectively. In accord with this, C-dominant CC/CT genotype was linked to higher plasma TGF-β1 level compared to TT genotype. One haplotype (TC) (-509T, +869C) was associated with an increased risk for ISR (OR = 1.48, 95% CI: 1.06-2.06, P = 0.010).The C allele of TGF-β1 869T/C polymorphism, correlated with high plasma TGF-β1 level, represented an independent risk factor for BMS-ISR in Chinese Han patients with coronary artery disease.(Int Heart J 2018; 59: 161-169)

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In Vivo Effect of TGF-β1

Cited by 109 publications

References 41 publications

Increased Flow and Shear Stress Enhance In Vivo Transforming Growth Factor-β1 After Experimental Arterial Injury

Increased Flow and Shear Stress Enhance In Vivo Transforming Growth Factor-β1 After Experimental Arterial Injury

Growth Factors Stimulate Neointimal Cells In Vitro and Increase the Thickness of the Neointima Formed at the Neck of Porcine Aneurysms Treated by Embolization

Role of Gene Polymorphisms/Haplotypes and Plasma Level of TGF-β1 in Susceptibility to In-Stent Restenosis Following Coronary Implantation of Bare Metal Stent in Chinese Han Patients

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