AI Article Synopsis
- Myocardial ischemia-reperfusion injury (MIRI) is when heart tissue gets damaged when blood flow returns after being blocked, which makes patients feel worse.
- Researchers found that a protein called HIF2α helps protect the heart during MIRI by controlling another protein called IL-6.
- When HIF2α was removed from mouse hearts, the damage got worse, but giving mice IL-6 helped protect their hearts, highlighting the importance of both proteins in heart health.
Article Abstract
Myocardial ischemia-reperfusion injury (MIRI) results in increased myocardial infarct size and leads to poor clinical outcomes. Hypoxia-inducible factor 2-alpha (HIF2α) exerts myocardial protective effects during MIRI through as yet unclear mechanisms. Here, we show that knockdown of HIF2α with cardiotropic recombinant adeno-associated virus serotype 9 (rAAV9) in mouse hearts significantly increased the infarct sizes during myocardial ischemia/reperfusion (MI/R). In addition, HIF2α transcriptionally regulated the expression of interleukin 6 (IL-6) in cardiomyocytes to elicit cardioprotection. Likewise, IL-6 deficiency aggravated MIRI, while treatment with recombinant IL-6 had cardioprotective effects and rescued the mice with HIF2α knockdown. Furthermore, IL-6 treatment significantly activated the PI3K/Akt and STAT3 signaling pathways in the myocardium during MI/R, and the specific inhibitors wortmannin (specific phosphoinositide 3-kinase inhibitor) and Stattic (specific STAT3 inhibitor) substantially abolished HIF2α/IL-6-induced cardioprotection. These studies suggest that HIF2α transcription regulates the expression of IL-6 in cardiomyocytes and plays a protective role during MI/R.
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|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906200 | PMC |
| http://dx.doi.org/10.18632/aging.202276 | DOI Listing |
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