A molecular protective mechanism for the clearance of haematomas

By Joe Boyle

Hematomas are a serious cardiovascular problem and are life-threatening in stroke. Heme from erythrocytes is cleared via Heme Oxygenase 1 (HO-1). HO-1 plays a key role in vascular homeostasis and its clinical genetic deficiency causes a fatal paediatric disease. However, the regulatory mechanisms for this pathway are only partially understood. We developed a novel and facile model of hematoma resolution to better understand the molecular regulation of HO-1 in vivo. In this study just published in Circulation Research, we show that hematoma clearance in vivo, and HO-1 induction by hemin, are mediated by Adenosine Monophosphate Activated Protein Kinase (AMPK) and by Activating Transcription Factor 1 (ATF1).

With Vascular Network colleagues in Chemistry we developed a novel strategy for tracking iron similar to fluorescent label tracing in biological systems. These fluorescent tracking studies indicated that AMPK and ATF1 actively partition iron and lipid into different macrophages. Their loss causes colocalisation of these metabolites, with oxidative stress and inflammation. Taken together, our findings provide insights into the mechanism of hematoma resolution and point to potential therapeutic pathways in hemorrhage-related diseases such as atherosclerosis and stroke.

Link to publication: https://pubmed.ncbi.nlm.nih.gov/32611235/

References

Seneviratne AN, Han Y, Wong E, Walter ER, Jiang L, Cave L, Long NJ, Carling D, Mason JC, Haskard DO and Boyle JJ. Hematoma Resolution In Vivo Is Directed by Activating Transcription Factor 1 (ATF1). Circ Res. 2020.