The roles of hypoxia signaling in cardiac remodeling

Abstract

Sterile inflammation develops in cardiac remodeling, where inflammatory cells or macrophages accumulate to a failing heart. The molecular processes, however, by which macrophages are activated in cardiac remodeling remain unclear. Hypoxia inducible factor (HIF) is a transcription factor which plays a critical role in a transcriptional response to hypoxia. We found that HIF signal regulates nitric oxide, an inflammatory mediator production in macrophages. HIF also activates macrophage migration capacity by upregulating glycolytic metabolism. Using animal model of cardiac hypertrophy and heart failure, we revealed that HIF in myeloid cells acts to prevent excessive fibrosis in a heart, illuminating the cardioprotective roles of HIF signaling.