Restenosis Following Angioplasty in the Swine Coronary Artery Is Inhibited By an Orally Active PDGF-Receptor Tyrosine Kinase Inhibitor, RPR101511A

Bilder, Glenda E.; Wentz, Tara; Leadley, Robert J.; Amin, Dilip; Byan, Lisa; O’Conner, Betsey; Needle, Saul; Galczenski, Helen; Bostwick, Jeffery; Kasiewski, Charles; Myers, Michael R.; Spada, Alfred P.; Merkel, Linda; Ly, Cuong Q.; Persons, P. E.; Page, K.R.; Perrone, Mark H.; Dunwiddie, Christopher T.

doi:10.1161/01.cir.99.25.3292

Cited by 78 publications

(41 citation statements)

References 30 publications

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“…Specifically, in different animal models of acute arterial injury by balloon catheterization, neointimal SMC accumulation was reduced by the administration of various PDGF pathway inhibitors, including neutralizing PDGF (AB) antibodies (Ferns et al 1991;Lewis et al 2001), PDGF-B aptamers (Leppänen et al 2000), PDGFR kinase inhibitors (Banai et al 1998;Yamasaki et al 2001), and PDGFR-neutralizing antibodies (Giese et al 1999;Hart et al 1999). Restenosis following angioplasty of atherosclerotic vessels in minipigs (Bilder et al 1999) and chronic cardiac transplant rejection-induced atherosclerosis in rats (Sihvola et al 1999) were also inhibited by PDGFR-blocking kinase inhibitors. In ApoE-deficient mice, atherosclerotic lesions were inhibited by neutralizing PDGFR-␤ antibodies (Sano et al 2001) and a PDGFR blocking kinase inhibitor (Kozaki et al 2002).…”

Section: Atherosclerosis and Restenosismentioning

confidence: 99%

Role of platelet-derived growth factors in physiology and medicine

Andræ¹,

Gallini²,

Betsholtz³

2008

Genes Dev.

2,074

1,898

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Platelet-derived growth factors (PDGFs) and their receptors (PDGFRs) have served as prototypes for growth factor and receptor tyrosine kinase function for more than 25 years. Studies of PDGFs and PDGFRs in animal development have revealed roles for PDGFR-␣ signaling in gastrulation and in the development of the cranial and cardiac neural crest, gonads, lung, intestine, skin, CNS, and skeleton. Similarly, roles for PDGFR-␤ signaling have been established in blood vessel formation and early hematopoiesis. PDGF signaling is implicated in a range of diseases. Autocrine activation of PDGF signaling pathways is involved in certain gliomas, sarcomas, and leukemias. Paracrine PDGF signaling is commonly observed in epithelial cancers, where it triggers stromal recruitment and may be involved in epithelial-mesenchymal transition, thereby affecting tumor growth, angiogenesis, invasion, and metastasis. PDGFs drive pathological mesenchymal responses in vascular disorders such as atherosclerosis, restenosis, pulmonary hypertension, and retinal diseases, as well as in fibrotic diseases, including pulmonary fibrosis, liver cirrhosis, scleroderma, glomerulosclerosis, and cardiac fibrosis. We review basic aspects of the PDGF ligands and receptors, their developmental and pathological functions, principles of their pharmacological inhibition, and results using PDGF pathway-inhibitory or stimulatory drugs in preclinical and clinical contexts.Platelet-derived growth factor (PDGF) was identified more than three decades ago as a serum growth factor for fibroblasts, smooth muscle cells (SMCs), and glia cells (Kohler and Lipton 1974;Ross et al. 1974;Westermark and Wasteson 1976). Human PDGF was originally identified as a disulfide-linked dimer of two different polypeptide chains, A and B, separable using reversed phase chromatography (Johnsson et al. 1982). The B-chain (PDGF-B) was characterized by amino acid sequencing, revealing a close homology between PDGF-B and the product of the retroviral oncogene v-sis of simian sarcoma virus (SSV) (Doolittle et al. 1983;Waterfield et al. 1983). Subsequent studies confirmed that the human cellular counterpart (c-sis) was identical to PDGF-B and that autocrine PDGF activity was sufficient for SSV transformation in vitro. This was a paradigm-shifting discovery about the relationship between neoplastic cell transformation and normal growth control. For the first time, the importance of autocrine growth stimulation in neoplastic transformation was demonstrated. As discussed below, it is now well established that autocrine PDGF stimulation plays a role also in some human cancers.PDGF-A was characterized by cDNA cloning ). This resolved a paradoxical lack of correlation between secretion of PDGF-like growth factors from tumor cell lines and their expression of c-sis; it turned out that most such cell lines express PDGF-A and secrete PDGF-AA homodimers ). Together with the demonstration that PDGF-BB homodimers are produced by SSV-transformed or PDGF-Bexpressing cells, these results showed that the PDGF...

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Section: Atherosclerosis and Restenosismentioning

confidence: 99%

Role of platelet-derived growth factors in physiology and medicine

Andræ¹,

Gallini²,

Betsholtz³

2008

Genes Dev.

2,074

1,898

View full text Add to dashboard Cite

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“…Although we have shown here that the in vitro responses of Harlan and Sasco CAVSMCs to growth and cytotoxic stimuli are entirely concordant with in vivo phenotypes of Harlan and Sasco rats in response to balloon vascular injury, the current data do not completely exclude the possibility that the phenotypic differences between Harlan and Sasco carotid arteries were also contributed by factors other than VSMCs, such as responses of platelets, leukocyte, coagulation cascades, and growth-factor production in the setting of vascular injury, all of which have been shown to play critical roles in the pathogenesis of restenosis (5,11,14,28,31). Nevertheless, the current work, to our knowledge, is the first to report restenosis-prone and -resistant rat substrains that originated from the same ancestrous strain (i.e., Sasco and Harlan Sprague-Dawley rats) and to suggest that a difference in the genetic (intrinsic) program on proliferation and cell death (Fig.…”

Section: Discussionmentioning

confidence: 54%

The critical role of the intrinsic VSMC proliferation and death programs in injury-induced neointimal hyperplasia

Mnjoyan

Doan

Brandon

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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“…12 Poly-L-lactic acid (185 kDa) biodegradable stents loaded with ST638 (0.8 mg), a specific tyrosine kinase inhibitor, were implanted in pig coronary arteries. After 3 weeks, the amount of neointimal proliferation was significantly decreased in the ST638 stents compared with its inactive metabolite (ST494).…”

Section: (C) Tyrosine Kinase Inhibitor-eluting Stentsmentioning

confidence: 99%