Abstract
Annexin A5 (AnxA5) is known to have anti-inflammatory and anti-apoptotic properties. Inflammation and apoptosis are key processes in post-ischemic cardiac remodeling. In this study, we investigated the effect of AnxA5 on left ventricular (LV) function and remodeling three weeks after myocardial ischemia-reperfusion (MI-R) injury in hypercholesterolemic ApoE*3-Leiden mice. Using a mouse model for MI-R injury, we demonstrate AnxA5 treatment resulted in a 27% reduction of contrast-enhanced MRI assessed infarct size (IS). End-diastolic and end-systolic volumes were decreased by 22% and 38%, respectively. LV ejection fraction was increased by 29% in the AnxA5 group compared to vehicle. Following AnxA5 treatment LV fibrous content after three weeks was reduced by 42%, which was accompanied by an increase in LV wall thickness of the infarcted area by 17%. Two days and three weeks after MI-R injury the number of cardiac macrophages was significantly reduced in both the infarct area and border zones following AnxA5 treatment compared to vehicle treatment. Finally, we found that AnxA5 stimulation leads to a reduction of IL-6 production in bone-marrow derived macrophages in vitro. AnxA5 treatment attenuates the post-ischemic inflammatory response and ameliorates LV remodeling which improves cardiac function three weeks after MI-R injury in hypercholesterolemic ApoE*3-Leiden mice.
Highlights
Acute myocardial infarction (MI) initiates a massive inflammatory response[1,2] and cell death[3]
This study shows a beneficial therapeutic effect of human recombinant annexin A5 (AnxA5) administration following Myocardial ischemia-reperfusion (MI-R) injury
AnxA5 treatment resulted in accumulation of AnxA5 in the infarct area subsequently leading to a reduced infarct size, most likely mediated by attenuation of the inflammatory response
Summary
Acute myocardial infarction (MI) initiates a massive inflammatory response[1,2] and cell death[3]. Through binding and ingestion of dying cells, myeloid cells can markedly influence immune responses by enhancing or suppressing inflammation indicating close interaction between cell death and inflammation[8] In line with this affecting apoptosis and inflammation to mitigate cellular damage might result in new clinical therapies. A reduced post-interventional inflammatory response was observed following AnxA5 treatment resulting in a potential therapeutic effect against post-interventional intimal hyperplasia[19] and accelerated atherosclerosis[20]. The anti-apoptotic and anti-inflammatory effects of AnxA5, can provide a possible role of human recombinant AnxA5 as a therapeutic agent to decrease post-ischemic left ventricular (LV) remodeling and improve cardiac function. We investigate the effect of AnxA5 treatment on the post ischemic-reperfused inflammatory response
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
