Ethan Italiano
Current Organizations / Institutes
The organizations/institutes from the scholar's latest article
Research Subjects
Ethan Italiano has a total of 22 co-authors. Here are the top co-authors by number of shared publications:
Alan Pham
Department of Anatomical Pathology, The Alfred Hospital, Melbourne, Australia
1 shared publication- Alexandra F. Sharland
Sydney Medical School, Faculty of Medicine and Health, University of Sydney, NSW 2006, Australia
1 shared publication Amy Rapkiewicz
New York University Winthrop Hospital, Department of Pathology, Long Island School of Medicine, Mineola, USA
1 shared publication- Andre Laval Samson
The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
1 shared publication - Eduardo A. Albornoz
School of Biomedical Sciences, University of Queensland, St Lucia, Australia
1 shared publication Imala Alwis
The Heart Research Institute, Sydney, Australia
1 shared publication
Latest Publications
- 4 June 2025
- Published by Springer Nature in Nature
- Vol. 643 (8070) , 182-191
Ischaemic endothelial necroptosis induces haemolysis and COVID-19 angiopathy
Microangiopathy is a major complication of SARS-CoV-2 infection and contributes to the acute and chronic complications of the disease1. Endotheliopathy and dysregulated blood coagulation are prominent in COVID-19 and are considered to be major causes of microvascular obstruction1,2. Here we demonstrate extensive endothelial cell (EC) death in the microvasculature of COVID-19 organs. Notably, EC death was not associated with fibrin formation or platelet deposition, but was linked to microvascular red blood cell (RBC) haemolysis. Importantly, this RBC microangiopathy was associated with ischaemia–reperfusion injury, and was prominent in the microvasculature of humans with myocardial infarction, gut ischaemia, stroke, and septic and cardiogenic shock. Mechanistically, ischaemia induced MLKL-dependent EC necroptosis and complement-dependent RBC haemolysis. Deposition of haemolysed RBC membranes at sites of EC death resulted in the development of a previously unrecognized haemostatic mechanism preventing microvascular bleeding. Exaggeration of this haemolytic response promoted RBC aggregation and microvascular obstruction. Genetic deletion of Mlkl from ECs decreased RBC haemolysis, microvascular obstruction and reduced ischaemic organ injury. Our studies demonstrate the existence of a RBC haemostatic mechanism induced by dying ECs, functioning independently of platelets and fibrin. Therapeutic targeting of this haemolytic process may reduce microvascular obstruction in COVID-19, and other major human diseases associated with organ ischaemia.
- 4 June 2025
- Published by Springer Nature in Nature
- Vol. 643 (8070) , 182-191
Ischaemic endothelial necroptosis induces haemolysis and COVID-19 angiopathy
Microangiopathy is a major complication of SARS-CoV-2 infection and contributes to the acute and chronic complications of the disease1. Endotheliopathy and dysregulated blood coagulation are prominent in COVID-19 and are considered to be major causes of microvascular obstruction1,2. Here we demonstrate extensive endothelial cell (EC) death in the microvasculature of COVID-19 organs. Notably, EC death was not associated with fibrin formation or platelet deposition, but was linked to microvascular red blood cell (RBC) haemolysis. Importantly, this RBC microangiopathy was associated with ischaemia–reperfusion injury, and was prominent in the microvasculature of humans with myocardial infarction, gut ischaemia, stroke, and septic and cardiogenic shock. Mechanistically, ischaemia induced MLKL-dependent EC necroptosis and complement-dependent RBC haemolysis. Deposition of haemolysed RBC membranes at sites of EC death resulted in the development of a previously unrecognized haemostatic mechanism preventing microvascular bleeding. Exaggeration of this haemolytic response promoted RBC aggregation and microvascular obstruction. Genetic deletion of Mlkl from ECs decreased RBC haemolysis, microvascular obstruction and reduced ischaemic organ injury. Our studies demonstrate the existence of a RBC haemostatic mechanism induced by dying ECs, functioning independently of platelets and fibrin. Therapeutic targeting of this haemolytic process may reduce microvascular obstruction in COVID-19, and other major human diseases associated with organ ischaemia.