Systemic immunosuppressive therapy inhibits in-stent restenosis in patients with renal allograft

Jung, Jae Hun; Min, Pil‐Ki; Kim, Jong Youn; Park, Sungha; Choi, Eui Young; Ko, Young Guk; Choi, Donghoon; Jang, Yangsoo; Shim, Won Heum; Cho, Seung Yun

doi:10.1002/ccd.20799

Cited by 3 publications

(2 citation statements)

References 45 publications

(59 reference statements)

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“…As GSK-3β is located at the focal point where multiple cell signals merge to control cell proliferation, apoptosis and migration, it represents a potential novel molecular target to treat vascular proliferative disease. Several studies have highlighted the importance of GSK-3β targets in controlling vSMC proliferation and apoptosis in vitro [5] and in vivo [2, 23]. One such target, Notch is known to play a putative role in dictating venous to arterial differentiation during embryogenesis [25] and the vascular response to injury [28].…”

Section: Discussionmentioning

confidence: 99%

Glycogen synthase kinase 3 beta positively regulates Notch signaling in vascular smooth muscle cells: role in cell proliferation and survival

et al. 2011

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The role of glycogen synthase kinase 3 beta (GSK-3β) in modulating Notch control of vascular smooth muscle cell (vSMC) growth (proliferation and apoptosis) was examined in vitro under varying conditions of cyclic strain and validated in vivo following changes in medial tension and stress. Modulation of GSK-3β in vSMC following ectopic expression of constitutively active GSK-3β, siRNA knockdown and pharmacological inhibition with SB-216763 demonstrated that GSK-3β positively regulates Notch intracellular domain expression, CBF-1/RBP-Jκ transactivation and downstream target gene mRNA levels, while concomitantly promoting vSMC proliferation and inhibiting apoptosis. In contrast, inhibition of GSK-3β attenuated Notch signaling and decreased vSMC proliferation and survival. Exposure of vSMC to cyclic strain environments in vitro using both a Flexercell™ Tension system and a novel Sylgard™ phantom vessel following bare metal stent implantation revealed that cyclic strain inhibits GSK-3β activity independent of p42/p44 MAPK and p38 activation concomitant with reduced Notch signaling and decreased vSMC proliferation and survival. Exposure of vSMC to changes in medial strain microenvironments in vivo following carotid artery ligation revealed that enhanced GSK-3β activity was predominantly localized to medial and neointimal vSMC concomitant with increased Notch signaling, proliferating nuclear antigen and decreased Bax expression, respectively, as vascular remodeling progressed. GSK-3β is an important modulator of Notch signaling leading to altered vSMC cell growth where low strain/tension microenvironments prevail.

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Section: Discussionmentioning

confidence: 99%

Glycogen synthase kinase 3 beta positively regulates Notch signaling in vascular smooth muscle cells: role in cell proliferation and survival

et al. 2011

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“…Among the oral drugs used to control vascular proliferative response after coronary angioplasty, the sirolimus showed the most promising results [25][26][27] . Arruda et al 28 observed that patients with kidney transplant in a regular immunosuppression regimen who were submitted to angioplasty had only moderate in-stent intimal proliferation.…”

Section: Oral Sirolimus and Vasomotor Functionmentioning

confidence: 99%

Impacto dos stents e do sirolimus por via oral na vasomotilidade coronariana dependente e independente do endotelio

Fernandes¹,

Dantas²,

Oliveira³

et al. 2012

Arq. Bras. Cardiol.

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Systemic application of sirolimus prevents neointima formation not via a direct anti-proliferative effect but via its anti-inflammatory properties

Daniel

Dutzmann

Brunsch

et al. 2017

International Journal of Cardiology

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Our findings show that systemic sirolimus treatment effectively prevents SMC and EC proliferation in vivo without directly affecting these cells. Instead, sirolimus prevents neointima formation and re-endothelialization by attenuating the inflammatory response after injury with secondary effects on SMC and EC proliferation. Thus, despite a similar net effect, the mechanisms of systemic sirolimus treatment are largely different from the local effects achieved after application of sirolimus-eluting stents.

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Systemic immunosuppressive therapy inhibits in-stent restenosis in patients with renal allograft

Cited by 3 publications

References 45 publications

Glycogen synthase kinase 3 beta positively regulates Notch signaling in vascular smooth muscle cells: role in cell proliferation and survival

Glycogen synthase kinase 3 beta positively regulates Notch signaling in vascular smooth muscle cells: role in cell proliferation and survival

Impacto dos stents e do sirolimus por via oral na vasomotilidade coronariana dependente e independente do endotelio

Systemic application of sirolimus prevents neointima formation not via a direct anti-proliferative effect but via its anti-inflammatory properties

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