Comparative transcriptome analysis to elucidate the therapeutic mechanism of colchicine against atrial fibrillation

Yue, Honghua; Liang, Weitao; Gu, Jun; Zhao, Xueshan; Zhang, Tailong; Qin, Xiaoli; Zhu, Guonian; Wu, Zhong

doi:10.1016/j.biopha.2019.109422

Cited by 18 publications

(20 citation statements)

References 44 publications

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“…Clinical trials have demonstrated the potential role of colchicine in reducing the occurrence of atrial fibrillation following catheter ablation and cardiac surgeries [ 50 ]. It has been postulated that the modulation of atrial fibrosis by colchicine is mediated by its effects on interleukin-17 and renin-related pathways [ 51 ]. In a trial of patients undergoing coronary artery bypass grafting, perioperative treatment with colchicine was associated with reduction in post-surgical constrictive pericarditis [ 52 ].…”

Section: Colchicinementioning

confidence: 99%

Benefits and adverse effects of hydroxychloroquine, methotrexate and colchicine: searching for repurposable drug candidates

2020

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Repurposing of antirheumatic drugs has garnered global attention. The aim of this article is to overview available evidence on the use of widely used antirheumatic drugs hydroxychloroquine, methotrexate and colchicine for additional indications. Hydroxychloroquine has endothelial stabilizing and anti-thrombotic effects. Its use has been explored as an adjunctive therapy in refractory thrombosis in antiphospholipid syndrome. It may also prevent recurrent pregnancy losses in the absence of antiphospholipid antibodies. Hydroxychloroquine favourably modulates atherogenic lipid and glycaemic profiles. Methotrexate has been tried for modulation of cardiovascular events in non-rheumatic clinical conditions, although a large clinical trial failed to demonstrate a benefit. Colchicine has been shown to successfully reduce the risk of recurrent cardiovascular events in a large multicentric trial. Potential antifibrotic effects of colchicine require further exploration. Hydroxychloroquine, methotrexate and colchicine are also being tried at different stages of the ongoing Coronavirus Disease 19 (COVID-19) pandemic for prophylaxis and treatment. While the use of these agents is being diversified, their adverse effects should be timely diagnosed and prevented. Hydroxychloroquine can cause retinopathy and rarely cardiac and auditory toxicity, retinopathy being dose and time dependent. Methotrexate can cause transaminitis, cytopenias and renal failure, particularly in acute overdoses. Colchicine can rarely cause myopathies, cardiomyopathy, cytopenias and transaminitis. Strong evidence is warranted to keep balance between benefits of repurposing these old antirheumatic drugs and risk of their adverse effects.

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Section: Colchicinementioning

confidence: 99%

Benefits and adverse effects of hydroxychloroquine, methotrexate and colchicine: searching for repurposable drug candidates

2020

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“…For example, proliferating cell nuclear antigen (PCNA) level increases in arrhythmia, and when chloroquine has an effect, it prevents PCNA increase (34). CD177 was reported to contribute to blocking atrial brillation (35). Chloroquine inhibits autophagy and promotes apoptosis, and METTL2, SHLD3, TP53BP1 are engaged nodes in these processes ( Table 2) (36)(37)(38).…”

Section: Discussionmentioning

confidence: 99%

Companion diagnostic for the chloroquine use in the treatment of COVID-19: systems biology report of candidate markers.

Souchelnytskyi

2020

Preprint

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BACKGROUND Chloroquine is used for the treatment of COVID-19 patients. However, efficacy of the chloroquine has been under discussion. Variability of clinical outputs of the drug application requires implementation of a companion diagnostic that would allow monitoring responsiveness to chloroquine. The first line of such markers would be markers already used in clinics. Analysis of reported mechanisms of COVID-19 and chloroquine may lead to such markers. METHODS Systemic analysis of molecular mechanisms and markers engaged by chloroquine and COVID-19 virus was performed. The networks of regulatory mechanisms were explored for an intersection and relevance to clinical markers. RESULTS Reported here systemic analysis describes the intersection of molecular mechanisms of chloroquine and processes engaged by COVID-19. 266 nodes provide insight into the mechanisms of chloroquine impact on the infection and represent a pool of companion diagnostic markers. As an example, an intersection with the markers of heart arrhythmia retrieved 19 nodes. Thirteen of them were reported in human plasma: levels of albumin, amyloid precursor protein, and endoglin correlate with adverse cardiac effects. CONCLUSIONS Reported nodes are the candidate markers for companion diagnostic of the chloroquine application to COVID-19 patients. Some of these markers are already used in the clinic and their interpretation may contribute to monitoring for adverse effects of chloroquine.

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“…CD177 was reported to contribute to blocking atrial brillation (35). Chloroquine inhibits autophagy and promotes apoptosis, and METTL2, SHLD3, TP53BP1 are engaged nodes in these processes ( Table 2) (36)(37)(38). Cardiomyocyte proliferation is regulated by another identi ed node, disabled homolog 2 (Dab2) (39).…”

Section: Discussionmentioning

confidence: 99%

Chloroquine use in the Treatment of COVID-19: Systems Biology Report of Common Targets of SARS-CoV-2 and Chloroquine.

Souchelnytskyi

2020

Preprint

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BACKGROUND: Chloroquine use for treatment of COVID-19 patients has been under discussion and recommendations have been shifting from positive to caution or non-conclusive. Variability of clinical outputs requires understanding of mechanisms of the differences. Implementation of a companion diagnostic would allow selecting patients who may benefit from the drug. The first line would be markers already used in clinics. Systems biology opens for an opportunity to identify targets common for chloroquine and SARS-CoV-2. These common targets would be candidates for the companion diagnostic.METHODS: Systemic analysis of molecular mechanisms and markers engaged by chloroquine and SARS-CoV-2 virus was performed. The networks of regulatory mechanisms were explored for an intersection and relevance to clinical markers.RESULTS: Reported here systemic analysis describes the intersection of molecular mechanisms of chloroquine and processes engaged by COVID-19. 266 nodes provide insight into the mechanisms of chloroquine impact on the infection and represent a pool of companion diagnostic markers. As an example, an intersection with the markers of heart arrhythmia retrieved 19 nodes. Thirteen of them were reported in human plasma: levels of albumin, amyloid precursor protein, and endoglin correlate with adverse cardiac effects. CONCLUSIONS: Reported intersection nodes of SARS-CoV-2 and chloroquine are the candidate markers for companion diagnostic of the chloroquine application. Some of these markers are already used in the clinic and their interpretation may contribute to monitoring for adverse effects of chloroquine.

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Comparative transcriptome analysis to elucidate the therapeutic mechanism of colchicine against atrial fibrillation

Cited by 18 publications

References 44 publications

Benefits and adverse effects of hydroxychloroquine, methotrexate and colchicine: searching for repurposable drug candidates

Benefits and adverse effects of hydroxychloroquine, methotrexate and colchicine: searching for repurposable drug candidates

Companion diagnostic for the chloroquine use in the treatment of COVID-19: systems biology report of candidate markers.

Chloroquine use in the Treatment of COVID-19: Systems Biology Report of Common Targets of SARS-CoV-2 and Chloroquine.

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