Abstract: The disruption of endothelial barrier integrity leading to increased vascular permeability contributes to many pathological processes. In a first cohort of 11 patients having cardiac arrest with vascular leakage, the inventors identified that AREG is 56-fold more expressed than control. During a second prospective clinical study, they confirmed a strong association between the plasma level of AREG and the fluid balance in 77 independent patients hospitalized for a cardiogenic shock. The inventors finally showed a crucial role for this protein in Areg?/? mice, with i) no KO-mice achieving a return of spontaneous circulation (ROSC) vs. 40% in WT mice (n=6 per group, p<0.05) and ii) a beneficial effect of 10 ?g recombinant AREG i.v. injection at the time of resuscitation, with 80% injected mice that achieve a ROSC vs 40% in controls (n=6, p<0.05). Finally, using markers of vascular extravasation, they demonstrated that AREG administration was decreasing the level of vascular leakage.

Abstract: Ischemic heart diseases are leading causes of death and reduced life quality worldwide. Although revascularization strategies significantly reduce mortality after acute myocardial infarction (MI), a large number of patients with MI develop chronic heart failure over time. The inventors previously reported that human recombinant ANGPTL4 counteracts ischemia-induced vascular endothelial growth factor signaling and disruption of endothelial cell junctions thus inhibiting vascular permeability. When administered before MI, the inventors could show that ANGPTL4 leads to protection of the coronary capillary network, reduction of no-reflow and infarct size in mice. The inventors also showed that the therapeutic effects observed with ANGPTL4 in ischemic conditions are not due to the CCD fragments but are brought by the FLD fragment (WO2016/110498).

Abstract: The present invention relates to methods and pharmaceutical compositions for the treatment of ischemic conditions. In particular, the present invention relates to a method of treating an ischemic condition in a subject in need thereof comprising administering the subject with a polypeptide comprising an amino acid sequence having at least 70% of identity with the amino acid sequence ranging from the amino acid residue at position 186 to the amino acid residue at position 406 in SEQ ID NO: 1.

Abstract: The present invention relates to methods and pharmaceutical compositions for the treatment of ischemic conditions. In particular, the present invention relates to a method of treating an ischemic condition in a subject in need thereof comprising administering the subject with a polypeptide comprising an amino acid sequence having at least 70% of identity with the amino acid sequence ranging from the amino acid residue at position 186 to the amino acid residue at position 406 in SEQ ID NO: 1.