Annexin A5 reduces infarct size and improves cardiac function after myocardial ischemia-reperfusion injury by suppression of the cardiac inflammatory response

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.

Pathogenetic features of morphodensitometric characteristics of cardiomyocytes and marker profile of the left ventricular remodeling in rats with experimental intermittent hypoxia of different duration

“…This fact suggested the physiological mode of cardiac muscle remodeling in rats of this group. In the case of long-term hypoxia, the content of annexin V was found to be 124.8 % higher than that in the control, which was a sign of significant cell death processes with the development of so-called myogenic dilation of the heart [18]. 2.…”

Effects on cardiac function, remodeling and inflammation following myocardial ischemia–reperfusion injury or unreperfused myocardial infarction in hypercholesterolemic APOE*3-Leiden mice

“…We showed limitation of LV remodeling demonstrated by a reduced infarct size, restricted LV dilation and preservation of LV wall thickness, as well as a different distributed inflammatory response following MI-R injury as compared to unreperfused MI, resembling the contemporary clinical outcome using rapid reperfusion more accurately. As well as unreperfused MI, MI-R injury still caused a significant impaired cardiac function, LV dilation and both local and systemic inflammatory response as compared to non-infarcted sham controls, making it suitable to study promising novel cardioprotective therapies in a clinically more relevant setting of rapid coronary reperfusion as we have shown before 40 .…”

A susceptibility biomarker identification strategy based on significantly differentially expressed ceRNA triplets for ischemic cardiomyopathy

“…The ICM susceptibility genes enriched in four ICM-related functional classes could classify samples accurately, including cardiovascular disease, which was associated with coronary angiogenesis and vascular endothelial growth factor receptor [41]; inflammatory immune, which was capable of causing myocardial ischemic injury [42]; metabolism, which was related to the phosphorylation of PI3K and Akt in myocardial tissue of cardiomyopathy [43], and cell polarity, one of the fundamental causes of congenital heart disease [44].…”