Thromboxane A&lt;sub&gt;2&lt;/sub&gt; Mediates Iron-Overload Cardiomyopathy in Mice Through Calcineurin-Nuclear Factor of Activated T Cells Signaling Pathway

Lin, Heng; Li, Hsiao Fen; Lian, Wei; Chen, Hsi Hsien; Lan, Yi; Lai, Pei Fang; Cheng, Ching Feng

doi:10.1253/circj.cj-12-1516

Cited by 21 publications

(19 citation statements)

References 41 publications

(31 reference statements)

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“…Using iron-overload mouse model, along with TXAS gene deleted mouse, recent study from Lin et al set out to elucidate the role of TXA 2 in cardiac iron-overload cardiomyopathy [54]. This study first demonstrated that iron loading can induce TXAS and its product TXB2 expression in mouse heart.…”

Section: Macrophage and Arachidonic Acid Associated Paracrine Pathmentioning

confidence: 99%

“…These findings suggest that TXA 2 may act as a paracrine facilitator of TNF- α expression. A recent study from Lin et al revealed that the addition of the TXA 2 agonist, U46619, to cardiac cultured cells can increase TNF- α expression [54]. This expression can be suppressed by BAPTA, CsA, and SQ29548, respectively.…”

Section: Other Beneficial Effects Against Ros and Inflammation In Iocmentioning

confidence: 99%

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Prooxidant Mechanisms in Iron Overload Cardiomyopathy

Cheng

Lian

2013

BioMed Research International

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Iron overload cardiomyopathy (IOC), defined as the presence of systolic or diastolic cardiac dysfunction secondary to increased deposition of iron, is emerging as an important cause of heart failure due to the increased incidence of this disorder seen in thalassemic patients and in patients of primary hemochromatosis. At present, although palliative treatment by regular iron chelation was recommended; whereas IOC is still the major cause for mortality in patient with chronic heart failure induced by iron-overloading. Because iron is a prooxidant and the associated mechanism seen in iron-overload heart is still unclear; therefore, we intend to delineate the multiple signaling pathways involved in IOC. These pathways may include organelles such as calcium channels, mitochondria; paracrine effects from both macrophages and fibroblast, and novel mediators such as thromboxane A2 and adiponectin; with increased oxidative stress and inflammation found commonly in these signaling pathways. With further understanding on these complex and inter-related molecular mechanisms, we can propose potential therapeutic strategies to ameliorate the cardiac toxicity induced by iron-overloading.

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Section: Macrophage and Arachidonic Acid Associated Paracrine Pathmentioning

confidence: 99%

Section: Other Beneficial Effects Against Ros and Inflammation In Iocmentioning

confidence: 99%

Prooxidant Mechanisms in Iron Overload Cardiomyopathy

Cheng

Lian

2013

BioMed Research International

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“…Inflammation is involved in many cardiovascular diseases, such as myocardial infarction, atherosclerosis, and cardiomyopathy [1][2][3]. In the process of inflammation, TNF-a is of great significance.…”

Section: Introductionmentioning

confidence: 99%

Lacidipine attenuates TNF-α-induced cardiomyocyte apoptosis

et al. 2015

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“…Alterations of the miR-122/CCL2 pathway may account for the inability of Vit.E to alleviate IO-induced hepatic inflammation because Vit.E intervention had no effect on the miR-122/CCL2 pathway. It has been reported that the intracellular iron content may affect the CCL2 expression in neuroblastoma and astrocytoma cell lines [24], rat aorta [25] and heart tissues [26], and mice cardiovascular systems [27]. Otogawa et al used an acute liver injury model that is induced by thioacetamide [28].…”

Section: Discussionmentioning

confidence: 99%

CCL2 is Upregulated by Decreased miR-122 Expression in Iron-Overload-Induced Hepatic Inflammation

Tang¹,

Jia²,

Niu³

et al. 2017

Cell Physiol Biochem

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Background/Aims: Iron overload (IO) is accompanied by hepatic inflammation. The chemokine (C-C motif) ligand 2 (CCL2) mediates inflammation, and its overexpression is associated with IO. However, whether IO results in CCL2 overexpression in the liver and the underlying mechanisms are unclear. Methods: We subjected mice to IO by administering intraperitoneal injections of dextran-iron or by feeding mice a 3% dextran-iron diet to observe the effects of IO on miR-122/CCL2 expression through real-time qPCR and Western blot analysis. We also used indicators, including the expression of the inflammatory cytokine, the inflammation score based on H&E staining and the serum content of ALT and AST to evaluate the effects of IO on hepatic inflammation. Meanwhile, we observed the effects of vitamin E on IO-induced hepatic inflammation. In cells, we used 100 µΜ FeSO₄ or 30 µΜ Holo-Tf to produce IO and observed the roles of miR-122 in regulating CCL2 expression by using miR-122 mimics or inhibitors to overexpress or inhibit miR-122. Then, we used a dual-luciferase reporter assay to prove that miR-122 regulates CCL2 expression through direct binding to its complementary sequence in the CCL2 mRNA 3’UTR. Results: IO induces the downregulation of miR-122 and the upregulation of CCL2, as well as inflammatory responses both in vitro and in vivo. Although IO-induced oxidative stress is eliminated by the antioxidant vitamin E, IO-induced hepatic inflammation still exists, which probably can be explained by the fact that vitamin E has no effects on the miR-122/CCL2 pathway. In in vitro experiments, the overexpression and inhibition of miR-122 significantly reduced and increased CCL2 expression, respectively. The dual-luciferase reporter assay indicates that miR-122 binds CCL2 mRNA 3’UTR. Conclusion: We propose the roles of miR-122/CCL2 in IO-induced hepatic inflammation. Our studies should provide a new clue for developing clinical strategies for patients with IO.

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Thromboxane A<sub>2</sub> Mediates Iron-Overload Cardiomyopathy in Mice Through Calcineurin-Nuclear Factor of Activated T Cells Signaling Pathway

Cited by 21 publications

References 41 publications

Prooxidant Mechanisms in Iron Overload Cardiomyopathy

Prooxidant Mechanisms in Iron Overload Cardiomyopathy

Lacidipine attenuates TNF-α-induced cardiomyocyte apoptosis

CCL2 is Upregulated by Decreased miR-122 Expression in Iron-Overload-Induced Hepatic Inflammation

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