Annexin A5 derived from lung alleviates brain damage after ischemic stroke.

Abstract

Ischemic stroke is a leading cause of disability and death worldwide. It is now accepted that brain interacts bidirectionally with other organs after brain diseases. However, factors that might mediate crosstalk between brain and other organs are still less reported. Here we reported that plasma level of Annexin A5, not Annexin A1 or A2, was upregulated in stroke patients when compared to controls. In normal mice, the highest level of Annexin A5 were detected in lung tissues compared with other major organs and lowest level in brain. Moreover, Annexin A5 was increased in brain and decreased in lung after stroke in mice when compared to sham group. Fluorescence in situ hybridization (FISH) assay indicated that Annexin A5 could penetrate the blood-brain barrier (BBB). Treatment with Annexin A5 recombinant protein reduced the infarct volumes and improved neurological function after stroke in mice, while administration of anti-Annexin A5 increased the infarct sizes and aggravated neurological function. In a proof-of-concept analysis, patients with both ischemic stroke and lung diseases had a lower plasma Annexin A5 level than those with only ischemic stroke. Furthermore, Annexin A5 level in bronchoalveolar lavage fluid (BALF) was lower in patients with severe chronic obstructive pulmonary disease (COPD) when compared with those at a less severe grade of COPD, and level of Annexin A5 was positively correlated with forced expiratory volume in 1 s/prediction (FEV1pred) and PaO2. Our results suggest that Annexin A5 could alleviate infarct area and improve general neurological performance post cerebral ischemia. Increased Annexin A5 may derive from lung tissue and permeate across BBB to provide a neuroprotective function. Therefore, Annexin A5 may potentially serve as a therapeutic candidate for defending against IS-induced brain injury.