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Prooxidant mechanisms in iron overload cardiomyopathy.

Cheng CF, Lian WS - Biomed Res Int (2013)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Research, Tzu Chi General Hospital and Department of Pediatrics, Tzu Chi University, Hualien, Taiwan ; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.

ABSTRACT
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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Involvement of multiple signaling pathways and cardiomyocyte-macrophage interactions in iron overload cardiomyopathy. The schematic diagram showed that iron can enter the cardiomyocytes through both L-type and T-type calcium channels and increased the ROS within cardiac cells. These effects then inhibit the calcium influx, impaired the excitation-contraction coupling and myofilaments contractility, and damage the intracellular organelles, including mitochondria. In addition, iron can activate the TXA2-TP receptor signaling pathway and promote cardiomyocyte-macrophage interaction. With G-CSF supplement, such macrophages recruitment and tissue factor induction will be enhanced, which further increased the ROS and gear up the inflammation-fibrosis circuit, result in aggravation of IOC and cardiac fibrosis.
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fig3: Involvement of multiple signaling pathways and cardiomyocyte-macrophage interactions in iron overload cardiomyopathy. The schematic diagram showed that iron can enter the cardiomyocytes through both L-type and T-type calcium channels and increased the ROS within cardiac cells. These effects then inhibit the calcium influx, impaired the excitation-contraction coupling and myofilaments contractility, and damage the intracellular organelles, including mitochondria. In addition, iron can activate the TXA2-TP receptor signaling pathway and promote cardiomyocyte-macrophage interaction. With G-CSF supplement, such macrophages recruitment and tissue factor induction will be enhanced, which further increased the ROS and gear up the inflammation-fibrosis circuit, result in aggravation of IOC and cardiac fibrosis.

Mentions: In this review, we delineated 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. Because iron is a prooxidant, the involved signaling pathways were associated with increased oxidative stress and inflammation. A schematic diagram (Figure 3) was depicted to show these complex and interrelated molecular mechanisms: iron can enter the cardiomyocytes through both L-type and T-type calcium channels and increased the ROS within cardiac cells. These effects then inhibit the calcium influx, impaired the excitation-contraction coupling and myofilaments contractility, and damage the intracellular organelles, including mitochondria. In addition, iron can activate the TXA2-TP receptor signaling pathway and promote cardiomyocyte-macrophage interaction. With G-CSF supplement, such macrophages recruitment and tissue factor induction will be enhanced, which further increased the ROS and gear up the inflammation-fibrosis circuit, result in aggravation of IOC and cardiac fibrosis. With further understanding on the molecular mechanisms involved in IOC, we propose the potential in using adiponectin, statins, and possible TNFα blockers for future therapeutic trials to ameliorate the cardiac toxicity induced by iron-overloading.


Prooxidant mechanisms in iron overload cardiomyopathy.

Cheng CF, Lian WS - Biomed Res Int (2013)

Involvement of multiple signaling pathways and cardiomyocyte-macrophage interactions in iron overload cardiomyopathy. The schematic diagram showed that iron can enter the cardiomyocytes through both L-type and T-type calcium channels and increased the ROS within cardiac cells. These effects then inhibit the calcium influx, impaired the excitation-contraction coupling and myofilaments contractility, and damage the intracellular organelles, including mitochondria. In addition, iron can activate the TXA2-TP receptor signaling pathway and promote cardiomyocyte-macrophage interaction. With G-CSF supplement, such macrophages recruitment and tissue factor induction will be enhanced, which further increased the ROS and gear up the inflammation-fibrosis circuit, result in aggravation of IOC and cardiac fibrosis.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3852805&req=5

fig3: Involvement of multiple signaling pathways and cardiomyocyte-macrophage interactions in iron overload cardiomyopathy. The schematic diagram showed that iron can enter the cardiomyocytes through both L-type and T-type calcium channels and increased the ROS within cardiac cells. These effects then inhibit the calcium influx, impaired the excitation-contraction coupling and myofilaments contractility, and damage the intracellular organelles, including mitochondria. In addition, iron can activate the TXA2-TP receptor signaling pathway and promote cardiomyocyte-macrophage interaction. With G-CSF supplement, such macrophages recruitment and tissue factor induction will be enhanced, which further increased the ROS and gear up the inflammation-fibrosis circuit, result in aggravation of IOC and cardiac fibrosis.
Mentions: In this review, we delineated 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. Because iron is a prooxidant, the involved signaling pathways were associated with increased oxidative stress and inflammation. A schematic diagram (Figure 3) was depicted to show these complex and interrelated molecular mechanisms: iron can enter the cardiomyocytes through both L-type and T-type calcium channels and increased the ROS within cardiac cells. These effects then inhibit the calcium influx, impaired the excitation-contraction coupling and myofilaments contractility, and damage the intracellular organelles, including mitochondria. In addition, iron can activate the TXA2-TP receptor signaling pathway and promote cardiomyocyte-macrophage interaction. With G-CSF supplement, such macrophages recruitment and tissue factor induction will be enhanced, which further increased the ROS and gear up the inflammation-fibrosis circuit, result in aggravation of IOC and cardiac fibrosis. With further understanding on the molecular mechanisms involved in IOC, we propose the potential in using adiponectin, statins, and possible TNFα blockers for future therapeutic trials to ameliorate the cardiac toxicity induced by iron-overloading.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Research, Tzu Chi General Hospital and Department of Pediatrics, Tzu Chi University, Hualien, Taiwan ; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus