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Angiopoietin-like 4 and ischaemic stroke: a promising start

Remo D. Spescha, Maria Sessa, Giovanni G. Camici
DOI: http://dx.doi.org/10.1093/eurheartj/eht183 First published online: 31 May 2013

This editorial refers to ‘Protective effects of angiopoietin-like 4 on cerebrovascular and functional damages in ischaemic stroke,’ by C. Bouleti et al., doi:10.1093/eurheartj/eht153

Stroke is a global cause of morbidity and mortality, ranking fourth among all causes of death.1 Although considerable progress has been made in developing effective tools for acute stroke treatment, at present the only drug approved is recombinant tissue plasminogen activator (rt-PA); thus, new strategies for its effective prevention and treatment are essential. Following ischaemia/reperfusion, the blood–brain barrier (BBB) becomes more permeable and, in doing so, it promotes an increased infiltration of pro-inflammatory cells, resulting in the so-called ‘reperfusion injury’.2 Given its key role in mediating ischaemia/reperfusion-related neuronal damage, the BBB is a central target for the development of novel therapeutical strategies.

Bouleti and colleagues have provided an elegant study reporting a new target improving stroke outcome in mice.3 Their study shows that angiopoietin-like 4 (ANGPTL4) modulates endothelial permeability following ischaemia/reperfusion and thus represents a potential new therapeutical target for the treatment of stroke.

ANGPTL4, first discovered in 2000, was originally classified as an adipokine playing roles in lipid metabolism.4 Over the last decade, ANGPTL4 has been recognized to play additional roles in tumorigenesis, angiogenesis, and redox regulation.4 Bouleti and colleagues investigated the role of ANGPTL4 in stroke by using a transient focal cerebral ischaemia murine model, where the middle cerebral artery was occluded for 1 h, followed by 24 h of reperfusion. Indeed, they could show that recombinant human ANGPTL4 (rhANGPTL4) treatment prior to the ischaemic episode greatly reduced the stroke size and consequent neurological deficit. To provide additional supporting evidence for the protective effects of ANGPTL4, Bouleti et al. analysed stroke outcome in ANGPTL4 knockout mice undergoing ischaemic stroke. Moreover, to translate their findings into a more clinically relevant …