Suggested mechanism of ERBB1 and cardioprotection during myocardial ischemia and reperfusion injury. During myocardial ischemia and reperfusion injury, the heart experiences significant hypoxia. Hypoxia stabilizes transcription factor hypoxia-inducible factor 2A (HIF2A), which is then recruited by RNA-binding protein 4 (RBM4) to the RNA hypoxia response element (rHRE). This complex initiates the translation of ErbB1 mRNA to produce ERBB1 protein. Also upregulated during myocardial injury is amphiregulin (AREG). HIF2A binds to the AREG promotor and increases the transcription of AREG gene. Finally, increased AREG protein binds to the increased ERBB1 receptors and activate important ERBB1 downstream signaling cascades, such as Akt, to provide cardioprotection.