Apelin-13 infusion salvages the peri-infarct region to preserve cardiac function after severe myocardial injury

Abstract

Background Apelin-13 (A13) regulates cardiac homeostasis. However, the effects and mechanism of A13 infusion after an acute myocardial injury (AMI) have not been elucidated. This study assesses the restorative effects and mechanism of A13 on the peri-infarct region in murine AMI model. Methods 51 FVB/N mice (12 weeks, 30 g) underwent AMI. A week following injury, continuous micro-pump infusion of A13 (0.5 μg/g/day) and saline was initiated for 4-week duration. Dual contrast MRI was conducted on weeks 1, 2, 3, and 5, consisting of delayed-enhanced and manganese-enhanced MRI. Four mice in each group were followed for an extended period of 4 weeks without further infusion and underwent MRI scans on weeks 7 and 9. Results A13 infusion demonstrated preserved LVEF compared to saline from weeks 1 to 4 (21.9 ± 3.2% to 23.1 ± 1.7%* vs. 23.5 ± 1.7% to 16.9 ± 2.8%, *p = 0.02), which persisted up to 9 weeks post-MI (+1.4%* vs. −9.4%, *p = 0.03). Mechanistically, dual contrast MRI demonstrated significant decrease in the peri-infarct and scar % volume in A13 group from weeks 1 to 4 (15.1 to 7.4% and 34.3 to 25.1%, p = 0.02, respectively). This was corroborated by significant increase in 5-ethynyl-2′-deoxyuridine (EdU+) cells by A13 vs. saline groups in the peri-infarct region (16.5 ± 3.1% vs. 8.1 ± 1.6%; p = 0.04), suggesting active cell mitosis. Finally, significantly enhanced mobilization of CD34+ cells in the peripheral blood and up-regulation of APJ, fibrotic, and apoptotic genes in the peri-infarct region were found. Conclusions A13 preserves cardiac performance by salvaging the peri-infarct region and may contribute to permanent restoration of the severely injured myocardium.

Apelin and stem cells: the role played in the cardiovascular system and energy metabolism

“…They enhance the number of progenitor cells in the heart of post‐MI mice more efficiently than BMCs (Li et al, ). Consistent with this report, Chung et al () demonstrated that apelin‐13 could mobilize progenitor cells and improve the cardiac function after an acute myocardial injury. Moreover, after stem cell transplantation, increase in apelin expression in the heart or in the plasma of patients suffering from heart failure is associated with tissue repair.…”

Myocardial Viability Imaging using Manganese‐Enhanced MRI in the First Hours after Myocardial Infarction

“…Previous studies have demonstrated the accuracy of MEMRI in delineating infarct size in experimental MI [37,39,41,52,53] and its usefulness in interrogating pathophysiology, [30,54,55] but none have investigated such early changes after coronary occlusion in comparison to LGE-MRI. Our data suggest that myocytes within the AAR rapidly stop internalizing Mn 2+ under ischemic conditions, while our T1 mapping results show increased Mn 2+ uptake in the viable myocardium remote from the infarct.…”

The impact of dietary tarragon (Artemisia dracunculus) on serum apelin, brain-derived neurotrophic factor, cardiac troponin concentrations and histopathology of liver tissue in laying hens housed at different stocking densities

“…Apelin-13 has a role in regulating the stress response with the BDNF by improving the HPA Axis and Hippocampal Glucocorticoid Receptor Dysfunctions (Dai et al 2018). Apelin has a protective effect against oxidative stress in heart myocardial cells as in many tissues (Chung et al 2016). Besides, the hormones apelin and BDNF also have regulatory roles in cardiac contraction (Szokodi et al 2002;Fulgenzi et al 2015).…”