Effects of Tranilast on Inflammasome and Macrophage Phenotype in a Mouse Model of Myocardial Infarction

Qu, Di; Guo, Huihui; Xu, Yanan

doi:10.1089/jir.2020.0208

Cited by 3 publications

(2 citation statements)

References 36 publications

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“…anakinra), 68 the NLR family pyrin domain containing three inflammasome (e.g. MCC950 and tranilast), 69 , 70 TNF-α (e.g. adalimumab), 71 IL-6 (e.g.…”

Section: Atheroprotective Strategies Targeting Inflammation and Immunitymentioning

confidence: 99%

Methotrexate and cardiovascular prevention: an appraisal of the current evidence

Mangoni,

Sotgia,

Zinellu

et al. 2023

Therapeutic Advances in Cardiovascular Disease

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New evidence continues to accumulate regarding a significant association between excessive inflammation and dysregulated immunity (local and systemic) and the risk of cardiovascular events in different patient cohorts. Whilst research has sought to identify novel atheroprotective therapies targeting inflammation and immunity, several marketed drugs for rheumatological conditions may serve a similar purpose. One such drug, methotrexate, has been used since 1948 for treating cancer and, more recently, for a wide range of dysimmune conditions. Over the last 30 years, epidemiological and experimental studies have shown that methotrexate is independently associated with a reduced risk of cardiovascular disease, particularly in rheumatological patients, and exerts several beneficial effects on vascular homeostasis and blood pressure control. This review article discusses the current challenges with managing cardiovascular risk and the new frontiers offered by drug discovery and drug repurposing targeting inflammation and immunity with a focus on methotrexate. Specifically, the article critically appraises the results of observational, cross-sectional and intervention studies investigating the effects of methotrexate on overall cardiovascular risk and individual risk factors. It also discusses the putative molecular mechanisms underpinning the atheroprotective effects of methotrexate and the practical advantages of using methotrexate in cardiovascular prevention, and highlights future research directions in this area.

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“…anakinra), 68 the NLR family pyrin domain containing three inflammasome (e.g. MCC950 and tranilast), 69 , 70 TNF-α (e.g. adalimumab), 71 IL-6 (e.g.…”

Section: Atheroprotective Strategies Targeting Inflammation and Immunitymentioning

confidence: 99%

Methotrexate and cardiovascular prevention: an appraisal of the current evidence

Mangoni,

Sotgia,

Zinellu

et al. 2023

Therapeutic Advances in Cardiovascular Disease

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show abstract

“…Moreover, recent studies showed that tranilast prevents doxorubicin-induced myocardial hypertrophy (10) and decreases myocardial fibrosis in diabetic rats via the TGF-β/SMAD signalling pathway (11). Furthermore, tranilast attenuates cerebral IR injury in rats via NF-κB and peroxisome proliferator-activated receptor-mediated inflammatory responses (12) and improves myocardial infarction in mice by inhibiting nucleotide binding oligomerization domain-like receptor family pyrin domain containing-3 inflammasome and affecting the phenotype of macrophages (13). However, to the best of our knowledge, the effect of tranilast on MIRI remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Tranilast reduces cardiomyocyte injury induced by ischemia‑reperfusion via Nrf2/HO‑1/NF‑κB signaling

Wang¹,

Shen²

2023

Exp Ther Med

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Tranilast, a synthetic derivative of a tryptophan metabolite, can be used to treat heart diseases. However, the specific mechanism underlying the effect of tranilast on ischemia-reperfusion (I/R) injury-induced cardiomyocyte apoptosis remains unclear. Therefore, the present study aimed to determine if tranilast could attenuate I/R-induced cardiomyocyte injury. A hypoxia/reoxygenation (H/R) model of H9c2 cardiomyocytes was established to simulate I/R-induced cardiomyocyte injury. The viability, apoptosis, inflammation and oxidative stress in H/R-induced H9c2 cells following treatment with tranilast were evaluated by Cell Counting Kit-8 and TUNEL assay. Commercially available kits were used to detect the levels of inflammatory markers and oxidative stress indicators. In addition, the expression levels of the apoptosisand nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1)/NF-κB signalling pathway-associated proteins were detected by western blotting. The levels of reactive oxygen species were determined using 2' ,7'-dichlorofluorescin diacetate assay kit. The viability of H9c2 cells was decreased following induction with H/R. However, treatment with tranilast increased viability while decreasing apoptosis, oxidative stress and inflammatory response in H/R-induced H9c2 cells by activating Nrf2/HO-1/NF-κB signalling.Furthermore, treatment with ML-385, an Nrf2 inhibitor, reversed the effects of tranilast on H/R-induced H9c2 cells. In conclusion, the results of the present study suggested that tranilast could attenuate I/R-induced cardiomyocyte injury via the Nrf2/HO-1/NF-κB signalling pathway.

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The Role of NLRP3 Inflammasome in Diabetic Cardiomyopathy and Its Therapeutic Implications

Ding

Song

et al. 2022

Oxidative Medicine and Cellular Longevity

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Diabetic cardiomyopathy (DCM) is a serious complication of diabetes mellitus (DM). However, the precise molecular mechanisms remain largely unclear, and it is still a challenging disease to diagnose and treat. The nucleotide-binding oligomerization domain and leucine-rich repeat pyrin 3 domain (NLRP3) inflammasome is a critical part of the innate immune system in the host to defend against endogenous danger and pathogenic microbial infections. Dysregulated NLRP3 inflammasome activation results in the overproduction of cytokines, primarily IL-1β and IL-18, and eventually, inflammatory cell death-pyroptosis. A series of studies have indicated that NLRP3 inflammasome activation participates in the development of DCM, and that corresponding interventions could mitigate disease progression. Accordingly, this narrative review is aimed at briefly summarizing the cell-specific role of the NLRP3 inflammasome in DCM and provides novel insights into developing DCM therapeutic strategies targeting the NLRP3 inflammasome.

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Effects of Tranilast on Inflammasome and Macrophage Phenotype in a Mouse Model of Myocardial Infarction

Cited by 3 publications

References 36 publications

Methotrexate and cardiovascular prevention: an appraisal of the current evidence

Methotrexate and cardiovascular prevention: an appraisal of the current evidence

Tranilast reduces cardiomyocyte injury induced by ischemia‑reperfusion via Nrf2/HO‑1/NF‑κB signaling

The Role of NLRP3 Inflammasome in Diabetic Cardiomyopathy and Its Therapeutic Implications

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