Ticagrelor Improves Remodeling, Reduces Apoptosis, Inflammation and Fibrosis and Increases the Number of Progenitor Stem Cells After Myocardial Infarction in a Rat Model of Ischemia Reperfusion

Birnbaum, Yochai; Tran, Dat Q.; Chen, Huan; Nylander, Sven; Sampaio, Luiz C.; Ye, Yumei

doi:10.33594/000000189

Cited by 21 publications

(8 citation statements)

References 42 publications

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“…In addition, ticagrelor improved EF 4 weeks after ischemia/reperfusion by attenuating fibrosis and decreasing the mRNA level of collagen-III, but clopidogrel did not. Moreover, ticagrelor decreased the levels of interleukin-1β, proinflammatory tumor necrosis factor-α, and interleukin-18, while increasing the levels of anti-inflammatory 15-epi-lipoxin-A4 [ 85 ], in agreement with other research [ 86 ]. To date, there has been no large randomized, double-blind, and multicenter research to investigate whether ticagrelor can improve myocardial remodeling after myocardial infarction.…”

Section: Reducing Ischemia-reperfusion Injury and Improving Cardiac F...supporting

confidence: 89%

A Review of the Role of the Antiplatelet Drug Ticagrelor in the Management of Acute Coronary Syndrome, Acute Thrombotic Disease, and Other Diseases

et al. 2022

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P2Y12 inhibitors, including aspirin, are key components of dual-antiplatelet therapy (DAPT), which is the optimal therapeutic strategy for preventing arterial thrombosis in patients with acute coronary syndromes (ACS) who underwent stent implantation. Ticagrelor is a cyclopentyl-triazole pyrimidine antiplatelet drug that was the first reversible oral P2Y12 receptor antagonist. Compared with clopidogrel, ticagrelor exerts a faster onset and offset of function by reversible and selective inhibition of platelet aggregation in ACS patients, including those with coronary artery blood revascularization. Despite improvement in stent materials, stent thrombosis (ST) due to high on-treatment platelet reactivity (HPR) to clopidogrel continues to occur. In addition to antiplatelet aggregation, ticagrelor displays pleiotropic cardioprotective effects, including improving coronary blood flow, reducing myocardial necrosis after an ischemic event, and anti-inflammatory effects. The benefits of ticagrelor over clopidogrel were consistent in the PLATO results, with lower incidence of the primary endpoint. Also, in 2020, the findings from the phase 3 THALES trial (NCT03354429) showed that aspirin combined with 90 mg of ticagrelor significantly reduced the rates of stroke and death compared with aspirin alone in patients with AIS or TIA. Here, we review recent research on the superiority of ticagrelor over clopidogrel, discuss the pharmacological mechanism, and present future perspectives. This review aims to present the roles of ticagrelor in the management of acute coronary syndrome, acute thrombotic disease, and other diseases.

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Section: Reducing Ischemia-reperfusion Injury and Improving Cardiac F...supporting

confidence: 89%

A Review of the Role of the Antiplatelet Drug Ticagrelor in the Management of Acute Coronary Syndrome, Acute Thrombotic Disease, and Other Diseases

et al. 2022

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“…According to the study by Birnbaum et al 29 , ticagrelor, possibly by inducing a local increase in extracellular adenosine levels, may augment reparative mechanisms that attenuate adverse remodeling and fibrosis, and it may increase cell proliferation and stem cell recruitment. Based on these data, it may provide an alternative approach to cardioprotection and stem cell therapy, as evidenced by improved cardiac function 29 .…”

Section: Discussionmentioning

confidence: 99%

Changes in cardiac cells due to ticagrelor and enoxaparin in a rat ischemia/reperfusion model

Findik

Barış

Yazır

et al. 2021

Rev. Assoc. Med. Bras.

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OBJECTIVE: Studies on ischemia/reperfusion injury remain the focus of interest. Ticagrelor and enoxaparin, which are antiaggregant and anticoagulant drugs developed for use in many cardiovascular pathologies, are still included in many ischemia/reperfusion studies.Remarkably, their new protective effects, especially with regard to ticagrelor, continue to be reported in the current literature. The aim of this study was to evaluate the beneficial effects of ticagrelor and enoxaparin pretreatments on the rat heart with histological and immunohistochemical markers in an ischemia/reperfusion model. METHODS:Wistar-albino rats (weighing 350-400 g) were divided into four groups as follows: Sham-Control (Group 1), Control-Saline+ischemia/reperfusion (Group 2), Ticagrelor+ischemia/reperfusion (Group 3), and Enoxaparin+ischemia/reperfusion (Group 4). The ischemia/reperfusion injury model was applied to Group 2, Group 3 and Group 4. Heart tissue sections were stained with hematoxylin and eosin for histological examinations. Caspase 3 immunostaining was evaluated to detect apoptosis in the heart tissue sections. RESULTS:Both pretreatments ameliorated the ischemic damage but especially tissue sections belonging to Group 3 were nearly similar to control levels. The results indicated that ischemia/reperfusion-induced myocardial damage was significantly increased in Group 2, whereas ticagrelor and enoxaparin pretreatments in Group 3 and Group 4 significantly decreased apoptotic scores and the histological appearance of the Group 3 close to the normal myocardium (p<0.001).CONCLUSION: As supported by histological findings in our study, ticagrelor and enoxaparin have protective properties for heart tissue in this ischemia/reperfusion injury model.

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“…These drugs bind to P2Y 12 , the adenosine diphosphate (ADP) receptor of platelets, and prevent blood coagulation ( 93 ). A recent study has shown that ticagrelor may have a positive effect in ameliorating pulmonary fibrosis in rats ( 96 ). Likewise, prasugrel may have positive effects on relieving hepatic fibrosis ( 90 ).…”

Section: Anticoagulants In Organ Fibrosismentioning

confidence: 99%

“…Likewise, prasugrel may have positive effects on relieving hepatic fibrosis ( 90 ). However, further research is necessary for these drugs to be used in human clinical trials as it is unclear, whether the effects in animal studies would be translatable to patients is unclear ( 96 ).…”

Section: Anticoagulants In Organ Fibrosismentioning

confidence: 99%

The Therapeutic Potential of Anticoagulation in Organ Fibrosis

Park

Song

et al. 2022

Front. Med.

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Fibrosis, also known as organ scarring, describes a pathological stiffening of organs or tissues caused by increased synthesis of extracellular matrix (ECM) components. In the past decades, mounting evidence has accumulated showing that the coagulation cascade is directly associated with fibrotic development. Recent findings suggest that, under inflammatory conditions, various cell types (e.g., immune cells) participate in the coagulation process causing pathological outcomes, including fibrosis. These findings highlighted the potential of anticoagulation therapy as a strategy in organ fibrosis. Indeed, preclinical and clinical studies demonstrated that the inhibition of blood coagulation is a potential intervention for the treatment of fibrosis across all major organs (e.g., lung, liver, heart, and kidney). In this review, we aim to summarize our current knowledge on the impact of components of coagulation cascade on fibrosis of various organs and provide an update on the current development of anticoagulation therapy for fibrosis.

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Ticagrelor Improves Remodeling, Reduces Apoptosis, Inflammation and Fibrosis and Increases the Number of Progenitor Stem Cells After Myocardial Infarction in a Rat Model of Ischemia Reperfusion

Abstract: This article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND). Usage and distribution for commercial purposes as well as any distribution of modified material requires written permission.

Cited by 21 publications

References 42 publications

A Review of the Role of the Antiplatelet Drug Ticagrelor in the Management of Acute Coronary Syndrome, Acute Thrombotic Disease, and Other Diseases

A Review of the Role of the Antiplatelet Drug Ticagrelor in the Management of Acute Coronary Syndrome, Acute Thrombotic Disease, and Other Diseases

Changes in cardiac cells due to ticagrelor and enoxaparin in a rat ischemia/reperfusion model

The Therapeutic Potential of Anticoagulation in Organ Fibrosis

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