PDGF-Receptor Tyrosine Kinase Blocker AG1295 Selectively Attenuates Smooth Muscle Cell Growth In Vitro and Reduces Neointimal Formation After Balloon Angioplasty in Swine

Banai, Shmuel; Wolf, Yehuda G.; Golomb, Gershon; Pearle, Andrew D.; Waltenberger, Johannes; Fishbein, Ilia; Schneider, Aviva; Gazit, Aviv; Perez, Louise; Huber, Rita; Lazarovichi, Galila; Rabinovich, Laura; Levitzki, Alexander; Gertz, S. David

doi:10.1161/01.cir.97.19.1960

Cited by 163 publications

(106 citation statements)

References 31 publications

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“…[31][32][33] Banai and co-workers reported that in vivo delivery of the PDGF-R-specific tyrphostin AG1295 caused a significant reduction (Ͼ80%) in the numbers of smooth muscle cells in the intima/media area of porcine femoral arteries after balloon injury. 31 Other investigators reported that administration of the PDGF-R-specific 2-phenylaminopyrimidine, CGP53716, inhibited an increase in intimal vascular smooth muscle cell number after balloon injury in rats by inhibiting both the migration and proliferation of smooth muscle cells. 33 At least one other blocking strategy that does not involve targeting tyrosine kinases has been reported.…”

Section: Discussionmentioning

confidence: 99%

Specific Inhibitors of Platelet-Derived Growth Factor or Epidermal Growth Factor Receptor Tyrosine Kinase Reduce Pulmonary Fibrosis in Rats

Rice

Moomaw

Morgan

et al. 1999

The American Journal of Pathology

135

107

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The proliferation of myofibroblasts is a central feature of pulmonary fibrosis. In this study we have used tyrosine kinase inhibitors of the tyrphostin class to specifically block autophosphorylation of the platelet-derived growth factor receptor (PDGF-R) or epidermal growth factor receptor (EGF-R). AG1296 specifically inhibited autophosphorylation of PDGF-R and blocked PDGF-stimulated [ 3 H]thymidine uptake by rat lung myofibroblasts in vitro. AG1478 was demonstrated as a selective blocker of EGF-R autophosphorylation and inhibited EGF-stimulated DNA synthesis in vitro. In a rat model of pulmonary fibrosis caused by intratracheal instillation of vanadium pentoxide (V 2 O 5 ) , intraperitoneal delivery of 50 mg/kg AG1296 or AG1478 in dimethylsulfoxide 1 hour before V 2 O 5 instillation and again 2 days after instillation reduced the number of epithelial and mesenchymal cells incorporating bromodeoxyuridine (Brdu) by ϳ50% at 3 and 6 days after instillation. V 2 O 5 instillation increased lung hydroxyproline fivefold 15 days after instillation , and AG1296 was more than 90% effective in preventing the increase in hydroxyproline , whereas AG1478 caused a 50% to 60% decrease in V 2 O 5 -stimulated hydroxyproline accumulation. These data provide evidence that PDGF and EGF receptor ligands are potent mitogens for collagen-producing mesenchymal cells during pulmonary fibrogenesis , and targeting tyrosine kinase receptors could offer a strategy for the treatment of fibrotic lung diseases. (Am J Pathol 1999, 155:213-221)

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Section: Discussionmentioning

confidence: 99%

Specific Inhibitors of Platelet-Derived Growth Factor or Epidermal Growth Factor Receptor Tyrosine Kinase Reduce Pulmonary Fibrosis in Rats

Rice

Moomaw

Morgan

et al. 1999

The American Journal of Pathology

135

107

View full text Add to dashboard Cite

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“…Each treatment was performed in triplicate with the cells being treated continuously for 9 days. The concentrations of angiogenic inhibitors used were based on IC 50 values and previously reported concentrations (Banai et al 1998, Kurimoto et al 2004, Hatziapostolou et al 2006, Sugiura et al 2007, Wang et al 2007. A further experiment was carried out to investigate the production of progesterone (nZ6 additional cultures).…”

Section: Effect Of Angiogenic Inhibitors On Endothelial Cell Network mentioning

confidence: 99%

FGF2 is crucial for the development of bovine luteal endothelial networks in vitro

Woad¹,

Hammond²,

Mann³

et al. 2009

Reproduction

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The development of the corpus luteum requires angiogenesis, and involves the complex interplay between factors such as vascular endothelial growth factor A (VEGFA), fibroblast growth factor 2 (FGF2) and platelet-derived growth factor (PDGF). However, the relative role of these factors remains to be elucidated. This study used a new physiologically relevant mixed luteal cell culture system to test the hypotheses that: a) FGF2 and VEGFA are critical for bovine luteal angiogenesis; and b) local luteal PDGF signalling stimulates the formation of endothelial networks. Cells were treated with receptor tyrosine kinase inhibitors against VEGFA (SU1498), FGF2 (SU5402) or PDGF (AG1295) activity. After 9 days in culture, endothelial cells were immunostained for von Willebrand factor (VWF) and quantified by image analysis. Highly organised intricate endothelial networks were formed in the presence of exogenous VEGFA and FGF2. The inhibition of FGF2 activity reduced the total area of VWF staining versus controls (O95%; P!0.001). Inhibition of VEGF and PDGF activity reduced the endothelial network formation by more than 60 and 75% respectively (P!0.05). Progesterone production increased in all treatments from day 1 to 7 (P!0.001), and was unaffected by FGF2 or PDGF receptor kinase inhibition (PO0.05), but was reduced by the VEGF receptor inhibitor on days 5 and 7 (P!0.001). In conclusion, this study confirmed that VEGF signalling regulates both bovine luteal angiogenesis and progesterone production. However, FGF2 was crucial for luteal endothelial network formation. Also, for the first time, this study showed that local luteal PDGF activity regulates bovine luteal endothelial network formation in vitro.

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“…With their low molecular weight and hydrophobic characteristics, tyrphostins can more easily gain access to receptor sites deep within tissues such as the arterial media (162). In vitro experiments have shown that the tyrphostin AGL-2043, as well as the related tyrphostin AG-1295, selectively inhibit PDGF receptors and selectively inhibit SMC proliferation in culture (163). Local delivery of AG-1295 by a perivascular polymeric matrix or intraluminally with nanoparticules inhibited intimal hyperplasia in a rat carotid injury model (164,165).…”

Section: Perlecanmentioning

confidence: 99%

The cell cycle: A critical therapeutic target to prevent vascular proliferative disease

Charron

Nili

Strauss

2006

Canadian Journal of Cardiology

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PDGF-Receptor Tyrosine Kinase Blocker AG1295 Selectively Attenuates Smooth Muscle Cell Growth In Vitro and Reduces Neointimal Formation After Balloon Angioplasty in Swine

Cited by 163 publications

References 31 publications

Specific Inhibitors of Platelet-Derived Growth Factor or Epidermal Growth Factor Receptor Tyrosine Kinase Reduce Pulmonary Fibrosis in Rats

Specific Inhibitors of Platelet-Derived Growth Factor or Epidermal Growth Factor Receptor Tyrosine Kinase Reduce Pulmonary Fibrosis in Rats

FGF2 is crucial for the development of bovine luteal endothelial networks in vitro

The cell cycle: A critical therapeutic target to prevent vascular proliferative disease

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