A Double Blind Randomized Study to Evaluate the Efficacy of Bindarit in Preventing Coronary Stent Restenosis

Colombo, Antonio; Limbruno, Ugo; Lettieri, Corrado; Lioy, Ernesto; Guglielmotti, Angelo; Calabresi, Marco; Valgimigli, Marco; Pierucci, Daniela

doi:10.1016/s0735-1097(12)60012-6

Cited by 2 publications

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“…It is effective in reducing neointimal formation in both non-hyperlipidemic and hyperlipidemic rodent models of vascular injury [16] as well as in a model of coronary in-stent stenosis in the pig [17] having a direct effect on VSMC proliferation/migration and reducing neointimal macrophage content [16] , [17] . Recently, a phase II clinical trial, has demonstrated the efficacy of bindarit in reducing in-stent late loss [18] . To better understand the effect of bindarit on human VSMC, here we evaluated the phenotypic modulation of CASMC analyzing the contractile proteins (α-SMA, calponin and SMemb) expression.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, we also demonstrated the efficacy of bindarit on in-stent stenosis in the preclinical porcine coronary stent model [17] . Importantly, a double-blind, randomized, placebo-controlled phase II clinical trial, with the aim of investigating the effect of bindarit in human coronary restenosis, showed that bindarit induced a significant reduction of in-stent late loss [18] . However, the mechanisms underlying the efficacy of bindarit in controlling neointimal formation/restenosis have not been fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

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Bindarit Inhibits Human Coronary Artery Smooth Muscle Cell Proliferation, Migration and Phenotypic Switching

et al. 2012

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Bindarit, a selective inhibitor of monocyte chemotactic proteins (MCPs) synthesis, reduces neointimal formation in animal models of vascular injury and recently has been shown to inhibit in-stent late loss in a placebo-controlled phase II clinical trial. However, the mechanisms underlying the efficacy of bindarit in controlling neointimal formation/restenosis have not been fully elucidated. Therefore, we investigated the effect of bindarit on human coronary smooth muscle cells activation, drawing attention to the phenotypic modulation process, focusing on contractile proteins expression as well as proliferation and migration. The expression of contractile proteins was evaluated by western blot analysis on cultured human coronary smooth muscle cells stimulated with TNF-α (30 ng/mL) or fetal bovine serum (5%). Bindarit (100–300 µM) reduced the embryonic form of smooth muscle myosin heavy chain while increased smooth muscle α-actin and calponin in both TNF-α- and fetal bovine serum-stimulated cells. These effects were associated with the inhibition of human coronary smooth muscle cell proliferation/migration and both MCP-1 and MCP-3 production. The effect of bindarit on smooth muscle cells phenotypic switching was confirmed in vivo in the rat balloon angioplasty model. Bindarit (200 mg/Kg/day) significantly reduced the expression of the embryonic form of smooth muscle myosin heavy chain, and increased smooth muscle α-actin and calponin in the rat carodid arteries subjected to endothelial denudation. Our results demonstrate that bindarit induces the differentiated state of human coronary smooth muscle cells, suggesting a novel underlying mechanisms by which this drug inhibits neointimal formation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Bindarit Inhibits Human Coronary Artery Smooth Muscle Cell Proliferation, Migration and Phenotypic Switching

et al. 2012

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The CCL2/CCR2 Axis in the Pathogenesis of HIV-1 Infection: A New Cellular Target for Therapy?

Covino¹,

Sabbatucci²,

Fantuzzi

2015

CDT

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The identification of chemokine receptors as necessary co-receptors for HIV entry into target cells represented a breakthrough in the understanding of the pathogenesis of this viral infection. Since this initial discovery, it was unraveled that chemokines, in addition to their role in blocking viral entry by binding to co-receptors, have other functions in HIV pathogenesis. Indeed, chemokines can either inhibit or enhance HIV replication, and these effects may involve both entry and post-entry events of the viral life cycle. Depending on the balance of their negative versus positive effects on HIV replication and spreading, chemokines contribute to different outcomes of HIV pathogenesis. CCL2 is unique among the chemokines in that mostly enhancing effects on viral replication and pathogenesis have been reported. Either HIV infection itself or exposure to viral products can induce the expression of this chemokine and of its receptor CCR2, and high levels of CCL2/CCR2 are indeed found in HIV-infected subjects. The CCL2/CCR2 axis is tightly linked to the high level of immune activation and inflammation that is the hallmark of HIV infection even in patients undergoing antiretroviral therapy. In addition, more direct effects of CCL2 on HIV replication are becoming apparent. Thus, modulation of CCL2/CCR2-driven effects may have significant impact on HIV disease progression. In this review, we will discuss the complex interaction between CCL2/CCR2 and HIV and the emerging therapeutic approaches based on the inhibition of this axis.

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A Double Blind Randomized Study to Evaluate the Efficacy of Bindarit in Preventing Coronary Stent Restenosis

Cited by 2 publications

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Bindarit Inhibits Human Coronary Artery Smooth Muscle Cell Proliferation, Migration and Phenotypic Switching

Bindarit Inhibits Human Coronary Artery Smooth Muscle Cell Proliferation, Migration and Phenotypic Switching

The CCL2/CCR2 Axis in the Pathogenesis of HIV-1 Infection: A New Cellular Target for Therapy?

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