Expression of platelet derived growth factor B chain and beta receptor in human coronary arteries after percutaneous transluminal coronary angioplasty: an immunohistochemical study.

Tanizawa, Shinichi; Ueda, Makiko; Loos, Chris M. van der; Wal, Allard C. van der; Becker, Anton E.

doi:10.1136/hrt.75.6.549

Cited by 77 publications

(56 citation statements)

References 25 publications

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“…In addition to reduction of PDGFR␤ autophosphorylation, tyrphostin treatment led to downregulation of receptor expression in the arterial wall after balloon injury. Because PDGFR␤-mediated signaling has been proven to play an important role in postangioplasty response in nonrodent mammals 10,27,28 and humans, 51,52 its specific inhibition represents a new and interesting approach that warrants further investigation.…”

Section: Discussionmentioning

confidence: 99%

Local Delivery of Platelet-Derived Growth Factor Receptor–Specific Tyrphostin Inhibits Neointimal Formation in Rats

Fishbein

Waltenberger

Banai

et al. 2000

ATVB

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Abstract-Signal transduction through the platelet-derived growth factor (PDGF)/PDGF receptor (PDGFR) system is involved in the process of postangioplasty restenosis. Tyrphostins are low molecular weight inhibitors of protein tyrosine kinases. We assessed the antiproliferative effects of PDGFR␤-specific tyrphostin AG-1295 in vitro and in vivo. AG-1295 significantly inhibited rat smooth muscle cell growth stimulated by PDGF-BB or FCS. This antiproliferative effect was paralleled by reversible reduction of the total phosphotyrosine level and the degree of PDGFR␤ phosphorylation by the drug in vitro. Local sustained delivery of the drug from perivascularly implanted polymeric matrices resulted in focal AG-1295 levels of 711 and 29.1 ng/mg of dry arterial tissue 1 and 14 days after implantation in rats. AG-1295 delivered from polymeric matrices resulted in a 35% reduction of neointimal formation on day 14 after balloon injury in the rat carotid model. Tyrosine phosphorylation of certain transduction proteins in arterial tissue extracts was significantly upregulated by balloon injury on day 3 but was essentially returned to or below basal levels 14 days after injury. Tyrphostin treatment decreased tyrosine phosphorylation at both time points below the basal levels. Moreover, the enhancement of PDGFR␤ expression 3 and 14 days after arterial injury was strongly inhibited by AG-1295 treatment. It can be concluded that AG-1295 reduces neointimal formation by inhibiting PDGF␤-triggered tyrosine phosphorylation.

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Section: Discussionmentioning

confidence: 99%

Local Delivery of Platelet-Derived Growth Factor Receptor–Specific Tyrphostin Inhibits Neointimal Formation in Rats

Fishbein

Waltenberger

Banai

et al. 2000

ATVB

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“…There are two PDGF receptors, PDGFR-␣ and PDGFR-␤, whose intrinsic tyrosine kinase activity is activated by PDGF-A alone, or PDGF-A and PDGF-B, respectively (36). The role of PDGF receptors has been described in several postinjury models (46), and it is reported that both PDGF chains and their receptors are detected in human coronary arteries following balloon angioplasty (249,256). Conventional knockout of PDGF-A (20), PDGF-B (141), PDGFR-␣ (241), and PDGFR-␤ (240) has been shown to result in early embryonic or perinatal lethality, thereby prohibiting use of these mice to investigate the role of PDGF signaling in vascular injury responses or experimental atherogenesis.…”

Section: Pdgfmentioning

confidence: 99%

Molecular Regulation of Vascular Smooth Muscle Cell Differentiation in Development and Disease

Owens

Kumar²,

Wamhoff³

2004

Physiological Reviews

3,034

3,134

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The focus of this review is to provide an overview of the current state of knowledge of molecular mechanisms/processes that control differentiation of vascular smooth muscle cells (SMC) during normal development and maturation of the vasculature, as well as how these mechanisms/processes are altered in vascular injury or disease. A major challenge in understanding differentiation of the vascular SMC is that this cell can exhibit a wide range of different phenotypes at different stages of development, and even in adult organisms the cell is not terminally differentiated. Indeed, the SMC is capable of major changes in its phenotype in response to changes in local environmental cues including growth factors/inhibitors, mechanical influences, cell-cell and cell-matrix interactions, and various inflammatory mediators. There has been much progress in recent years to identify mechanisms that control expression of the repertoire of genes that are specific or selective for the vascular SMC and required for its differentiated function. One of the most exciting recent discoveries was the identification of the serum response factor (SRF) coactivator gene myocardin that appears to be required for expression of many SMC differentiation marker genes, and for initial differentiation of SMC during development. However, it is critical to recognize that overall control of SMC differentiation/maturation, and regulation of its responses to changing environmental cues, is extremely complex and involves the cooperative interaction of many factors and signaling pathways that are just beginning to be understood. There is also relatively recent evidence that circulating stem cell populations can give rise to smooth muscle-like cells in association with vascular injury and atherosclerotic lesion development, although the exact role and properties of these cells remain to be clearly elucidated. The goal of this review is to summarize the current state of our knowledge in this area and to attempt to identify some of the key unresolved challenges and questions that require further study.

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“…The most potent SMC mitogen released at the site of injury by platelets, endothelial cells, and SMCs themselves is platelet-derived growth factor (PDGF). [1][2][3][4][5][6][7] PDGF is a disulfide-linked dimer of 2 related polypeptide chains, designated A and B, which are assembled as heterodimers (PDGF AB) or homodimers (PDGF AA and PDGF BB). 8 -10 PDGF exerts its biological activity by binding to alpha or beta PDGF receptors (PDGFRs), causing receptor dimerization and induction of intrinsic tyrosine kinase activity.…”

mentioning

confidence: 99%

The Role of Alpha and Beta Platelet-Derived Growth Factor Receptor in the Vascular Response to Injury in Nonhuman Primates

Giese

Marijianowski²,

McCook³

et al. 1999

ATVB

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Abstract-Restenosis remains a significant clinical problem associated with mechanical interventional procedures for arterial revascularization or repair, including coronary angioplasty and stenting. Studies with rodents have established that platelet-derived growth factor (PDGF), a potent chemotactic and mitogenic agent for vascular smooth muscle cells, is a key mediator of lesion formation after vascular injury. To further explore this hypothesis in a more clinically relevant model, neutralizing monoclonal antibodies (mAbs) were used to examine the effect of selective inhibition of alpha or beta PDGF receptor (PDGFR) on neointima formation in nonhuman primates. Carotid arteries were injured by surgical endarterectomy and femoral arteries by balloon catheter dilatation. Immunostaining revealed that both injuries induced cell proliferation and the upregulation of beta PDGFR but not alpha PDGFR. By 7 days after injury, beta PDGFR staining was limited to the luminal region of the media, the small areas of neointima, and the adventitia. Nearly all bromodeoxyuridine-positive cells were found in these regions as well. After 30 days, a concentric neointima that stained strongly for beta PDGFR had formed in the carotid and femoral arteries. Treatment of baboons with anti-beta PDGFR mAb 2A1E2 for 6 days after injury reduced the carotid artery and femoral artery lesion sizes by 37% (PϽ0.05) and 48% (PϽ0.005), respectively, when measured at 30 days. Under the same conditions, treatment with anti-alpha PDGFR mAb 2H7C5 had no effect. These findings suggest that PDGF mediates neointima formation through the beta PDGFR, and that antagonism of this pathway may be a promising therapeutic strategy for reducing clinical restenosis.

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Expression of platelet derived growth factor B chain and beta receptor in human coronary arteries after percutaneous transluminal coronary angioplasty: an immunohistochemical study.

Abstract: Objective-To evaluate whether expression of platelet derived growth factor B (PDGF-B) protein is associated with expression of its receptor protein in human coronary arteries after angioplasty and to identify cells involved. Background-PDGF is considered an

Cited by 77 publications

References 25 publications

Local Delivery of Platelet-Derived Growth Factor Receptor–Specific Tyrphostin Inhibits Neointimal Formation in Rats

Local Delivery of Platelet-Derived Growth Factor Receptor–Specific Tyrphostin Inhibits Neointimal Formation in Rats

Molecular Regulation of Vascular Smooth Muscle Cell Differentiation in Development and Disease

The Role of Alpha and Beta Platelet-Derived Growth Factor Receptor in the Vascular Response to Injury in Nonhuman Primates

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