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| Content Provider | Springer Nature Link |
|---|---|
| Author | Liu, Ying Templeton, Douglas M. |
| Copyright Year | 2001 |
| Abstract | Iron deposits preferentially in myocytes in mixed cultures of cardiac myocytes and nonmyocytic fibroblasts. In vivo, iron overload is associated with cardiac fibrosis. Therefore, we examined whether iron loading of cardiac myocytes in culture could trigger a response in nonmyocytes characteristic of a fibrogenic phenotype. We found that the nonmyocytes adopted a myofibroblast phenotype in culture. The rate of DNA synthesis (measured by [$^{3}$H]thymidine incorporation) by the nonmyocytes was decreased by the myocyte-conditioned medium, compared to that of the unconditioned medium, and this activity was retained in >10-kDa fractions. The rate was partially restored when the medium was obtained from iron-loaded myocytes, and in this medium, the >10-kDa fraction was even more effective in reversing the suppression of proliferation. This suppression suggests a decreased secretion of a growth-inhibitory substance in the iron-loaded myocytes, and this effect was partially reversed when the iron-loaded cells were treated with the iron chelator, deferoxamine. This indicates that cardiac myocytes may play a paracrine role in suppressing the proliferation of myofibroblasts that is partially overcome when the myocytes are iron overloaded. The myocyte-conditioned medium also affects the myofibroblast phenntype, increasing the cells' fibronectin mRNA content and decreasing α-smooth-muscle actin mRNA. The myocyte-conditioned medium increases transforming growth factor-β (TGF-β) secretion by myofibroblasts, but the TGF-β content of the conditioned medium was found to play, at most, a minor role in determining the response of the myofibroblast. |
| Starting Page | 299 |
| Ending Page | 308 |
| Page Count | 10 |
| File Format | |
| ISSN | 15307905 |
| Journal | Cardiovascular Toxicology |
| Volume Number | 1 |
| Issue Number | 4 |
| e-ISSN | 15590259 |
| Language | English |
| Publisher | Humana Press |
| Publisher Date | 2001-01-01 |
| Publisher Place | Totowa |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Iron overload iron toxicity cardiac myocytes myofibroblasts fibrosis TGF-β iron chelation Pharmacology/Toxicology Cardiology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Molecular Biology Toxicology Cardiology and Cardiovascular Medicine |
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