| First Author | Shao Y | Year | 2024 |
| Journal | Nat Cardiovasc Res | Volume | 3 |
| Issue | 1 | Pages | 28-45 |
| PubMed ID | 39195894 | Mgi Jnum | J:359890 |
| Mgi Id | MGI:7782851 | Doi | 10.1038/s44161-023-00392-x |
| Citation | Shao Y, et al. (2024) ATF3 coordinates the survival and proliferation of cardiac macrophages and protects against ischemia-reperfusion injury. Nat Cardiovasc Res 3(1):28-45 |
| abstractText | Cardiac resident MerTK(+) macrophages exert multiple protective roles after ischemic injury; however, the mechanisms regulating their fate are not fully understood. In the present study, we show that the GAS6-inducible transcription factor, activating transcription factor 3 (ATF3), prevents apoptosis of MerTK(+) macrophages after ischemia-reperfusion (IR) injury by repressing the transcription of multiple genes involved in type I interferon expression (Ifih1 and Ifnb1) and apoptosis (Apaf1). Mice lacking ATF3 in cardiac macrophages or myeloid cells showed excessive loss of MerTK(+) cardiac macrophages, poor angiogenesis and worse heart dysfunction after IR, which were rescued by the transfer of MerTK(+) cardiac macrophages. GAS6 administration improved cardiac repair in an ATF3-dependent manner. Finally, we showed a negative association of GAS6 and ATF3 expression with the risk of major adverse cardiac events in patients with ischemic heart disease. These results indicate that the GAS6-ATF3 axis has a protective role against IR injury by regulating MerTK(+) cardiac macrophage survival and/or proliferation. |
