We have located links that may give you full text access.
Hypoxia Inducible Factor-2α enhances neutrophil survival to promote cardiac injury following myocardial infarction.
American Journal of Physiology. Heart and Circulatory Physiology 2024 September 27
Heart failure is a major cause of mortality following myocardial infarction. Neutrophils are among the first immune cells to accumulate in the infarcted region. While beneficial functions of neutrophils in heart injury are now appreciated, neutrophils are also well-known for their ability to exacerbate inflammation and promote tissue damage. Myocardial infarction induces hypoxia, where hypoxia-inducible factors (HIFs) are activated and play critical roles in cellular functions. In this context the role of Hif2α in neutrophils during myocardial infarction is unknown. Here, we reveal in experimental mice that neutrophil Hif2α deletion substantially attenuated myocardial infarction size, improved cardiac systolic function, and reduced survival and accumulation of tissue infiltrated neutrophils. Mechanistic studies revealed that Hif2α promotes neutrophil survival through binding to hypoxia response element in the promoter region of Birc2 to regulate expression of the pro-survival protein cellular inhibitor of apoptosis protein-1 (cIAP1). Inhibition of cIAP1 in neutrophils using the pharmacological agent, Birinapant resulted in increased cell death, establishing a critical role of cIAP1 downstream of Hif2α in neutrophil survival. Taken together, our data demonstrate a protective effect of Hif2α deletion in neutrophils on cardiac injury outcomes through modulation of neutrophil cell survival.
Full text links
Related Resources
Trending Papers
Catastrophic Antiphospholipid Syndrome: A Review of Current Evidence and Future Management Practices.Curēus 2024 September
Oxygen therapy and noninvasive respiratory supports in acute hypoxemic respiratory failure: a narrative review.Annals of Intensive Care 2024 October 18
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app