Regulation of SLC19A3 thiamin transporter by HIF-1α

Abstract

Hypoxia-inducible factor 1 (HIF-1) is a master transcription factor that regulates gene expression in response to hypoxia, including SLC19A3, thiamine transporter 2, a facilitative carrier that mediates intracellular uptake of thiamin across the plasma membrane. Thiamin plays a significant role in energy production, which is required for myocardial contraction. In addition, thiamin deficiency (TD) induces heart complications that lead to heart failure as observed in type 2 diabetics, who are prone to be susceptible to ischemic complications. These studies suggested that HIF-1 enhances the expression of the thiamine transporter expression in H9c2 cardiomyocytes. Our initial findings led us to hypothesize that the HIF-1α-SLC19A3 signaling axis could be a cardioprotective therapeutic target against myocardial ischemia-reperfusion injury. Our results indicate that thiamin administration minimized infarction size when compared to control groups. However, further studies are required to elucidate the mechanistic potential of thiamin in treatment and prevention of myocardial ischemia-reperfusion injury.