Effects of ticagrelor on neointimal hyperplasia and endothelial function, compared with clopidogrel and prasugrel, in a porcine coronary stent restenosis model

Kim, Hyun Kuk; Jeong, Myung Ho; Lim, Kyung Seob; Kim, Jung Ha; Lim, Han Chul; Kim, Min Chul; Hong, Young Joon; Kim, Sung Soo; Park, Keun-Ho; Chang, Kyoung-Sig

doi:10.1016/j.ijcard.2017.04.108

Cited by 22 publications

(16 citation statements)

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“…48 Ticagrelor is known to be linked with the inhibition of SMC proliferation and, thus, reduced neointimal hyperplasia. [49][50][51] The results of this study further provide evidence of ticagrelor's beneficial inhibition of neointimal hyperplasia and preservation of endothelialization.…”

Section: Effects Of Ticagrelor On Endothelial Regeneration and Smcs Isupporting

confidence: 54%

Promoting vascular healing using nanofibrous ticagrelor-eluting stents

Lee

Hsieh

Liu

et al. 2018

IJN

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ObjectiveThe current treatment of atherosclerotic coronary heart disease with limus-eluting stents can lead to incomplete endothelialization and substantial impairment of arterial healing relative to treatment with bare-metal stents. The sustained and local delivery of ticagrelor, a reversibly binding P2Y12 receptor inhibitor, using hybrid biodegradable nanofibers/stents, was developed to reduce neointimal formation and endothelial dysfunction.MethodsIn this investigation, a solution of ticagrelor, poly(D,L)-lactide-co-glycolide, and hexafluoro isopropanol was electrospun to fabricate ticagrelor-eluting nanofibrous drug-eluting stents. The in vitro and in vivo ticagrelor concentrations were measured using a high-performance liquid chromatography assay. The effectiveness of ticagrelor-eluting stents was examined relative to that of sirolimus-eluting stents.ResultsAdequate ticagrelor levels were detected for four weeks in vitro. Less HES5-positive labeling was found near the ticagrelor-eluting stented vessels (0.33±0.12) than close to the sirolimus-eluting stented vessels (0.57±0.15) (p<0.05). Four weeks after deployment, the ticagrelor-eluting stent also exhibited an up-regulated local expression of SOD1 in the stenting area (p<0.001). The ticagrelor-eluting stent substantially preserved endothelial function and re-endothelialization, minimized inflammatory responses, and inhibited neointimal hyperplasia.ConclusionTicagrelor-eluting stents may provide an alternative route for treating patients at a high risk of bleeding to preserve endothelial recovery and to reduce smooth muscle proliferation.

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Section: Effects Of Ticagrelor On Endothelial Regeneration and Smcs Isupporting

confidence: 54%

Promoting vascular healing using nanofibrous ticagrelor-eluting stents

Lee

Hsieh

Liu

et al. 2018

IJN

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“…Ticagrelor is one of the most powerful P2Y 12 inhibitor (Motovska et al, 2018 ). Unlike other P2Y 12 inhibitors, ticagrelor exerts some pleiotropic effects acting mainly on endothelial function in several settings (Schnorbus et al, 2014 ; Li et al, 2016 ; Campo et al, 2017 ; Kim et al, 2017 ). In a recent randomized clinical trial, in patients with concomitant stable coronary artery disease (SCAD) and chronic obstructive pulmonary disease (COPD) undergoing percutaneous coronary intervention (PCI), we demonstrated that 1 month treatment with ticagrelor, as compared to clopidogrel, is associated with an improvement in markers of endothelial function, such as a reduction of endothelial apoptosis and endothelial nitric oxide (NO) production, a reduction in ROS levels in PBMC as well as a more effective reduction of platelet reactivity (Campo et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Ticagrelor Improves Endothelial Function by Decreasing Circulating Epidermal Growth Factor (EGF)

et al. 2018

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Ticagrelor is one of the most powerful P2Y12 inhibitor. We have recently reported that, in patients with concomitant Stable Coronary Artery Disease (SCAD) and Chronic Obstructive Pulmonary Disease (COPD) undergoing percutaneous coronary intervention (PCI), treatment with ticagrelor, as compared to clopidogrel, is associated with an improvement of the endothelial function (Clinical Trial NCT02519608). In the present study, we showed that, in the same population, after 1 month treatment with ticagrelor, but not with clopidogrel, there is a decrease of the circulating levels of epidermal growth factor (EGF) and that these changes in circulating levels of EGF correlate with on-treatment platelet reactivity. Furthermore, in human umbilical vein endothelial cells (HUVEC) incubated with sera of the patients treated with ticagrelor, but not with clopidogrel there is an increase of p-eNOS levels. Finally, analyzing the changes in EGF and p-eNOS levels after treatment, we observed an inverse correlation between p-eNOS and EGF changes only in the ticagrelor group. Causality between EGF and eNOS activation was assessed in vitro in HUVEC where we showed that EGF decreases eNOS activity in a dose dependent manner. Taken together our data indicate that ticagrelor improves endothelial function by lowering circulating EGF that results in the activation of eNOS in the vascular endothelium.

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“…32,33 The use of ticagrelor has been found in many studies to be superior to other antiplatelet therapies, including aspirin, clopidogrel and prasugrel with respect to platelet inhibition and reducing inflammation, endothelial function or fibrosis. 20,21,27,34 This indicates that ticagrelor is a potent treatment to reduce the cardiovascular risk and inhibit the development of DN in diabetic patients.…”

Section: Discussionmentioning

confidence: 99%

Platelet inhibition by ticagrelor is protective against diabetic nephropathy in mice

et al. 2020

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Diabetic nephropathy (DN) is a major complication of diabetes and is associated with high risk for cardiovascular mortality, which is partially related to elevated platelet activity. Platelets are also active players in inflammation and fibrosis. In this study, we examine the effect of ticagrelor‐induced platelet inhibition on the development of DN. DN was induced by unilateral nephrectomy followed by streptozotocin injections for 5 days. Mice received ticagrelor (300 mg/kg) or vehicle every other day, for 16 weeks. Experimental groups: non‐diabetic control, diabetic control, non‐diabetic ticagrelor, and diabetic ticagrelor. Ticagrelor treatment in diabetic mice lowered urinary albumin excretion, it prevented diabetes‐induced mesangial matrix expansion, podocyte effacement, and glomerular endothelial cell injury, which includes loss of endothelial fenestrations, ICAM‐1 expression, and PECAM expression. In addition, ticagrelor treatment prevented collagen IV deposition and macrophage infiltration in the tubulointerstitium and these diabetic mice showed lower systemic and tubular inflammation and tubular apoptosis. This tubular protection is likely to be a result of protection to the glomerular endothelium by ticagrelor, which reduces albuminuria and albumin toxicity to the tubules and reduced tubular and interstitial inflammation and fibrosis. In conclusion, ticagrelor‐induced platelet inhibition protects against renal injury in diabetic mice, likely by protecting the glomerular endothelial cells.

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Effects of ticagrelor on neointimal hyperplasia and endothelial function, compared with clopidogrel and prasugrel, in a porcine coronary stent restenosis model

Cited by 22 publications

References 54 publications

Promoting vascular healing using nanofibrous ticagrelor-eluting stents

Promoting vascular healing using nanofibrous ticagrelor-eluting stents

Ticagrelor Improves Endothelial Function by Decreasing Circulating Epidermal Growth Factor (EGF)

Platelet inhibition by ticagrelor is protective against diabetic nephropathy in mice

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