Abstract 4373610: Effect of combined guideline-directed medical therapy and mitochondria-rich extracellular vesicles in a mouse infarct model
Abstract
Introduction:
Beta blockers, renin-angiotensin-aldosterone antagonists, and mineralocorticoid antagonists are mainstays of current guideline-directed medical therapy (GDMT) in heart failure with reduced left ventricular ejection fraction (LVEF). GDMT has been hypothesized to interact and have protective effects in bioenergetics in cardiac injury by reducing cardiac workload and energy demand. We have previously demonstrated in a human-induced pluripotent stem cell-derived cardiomyocytes (iCMs) hypoxia model that treatment with GDMT plus mitochondrial-rich extracellular vesicles (M-EVs) improves cell viability. Here, we demonstrate the effect of GDMT and M-EV treatment in an established mouse LAD-infarct model.
Methods:
A total of 16 CD1 mice (50% female and male) underwent left anterior descending artery (LAD) injury, divided into 4 groups plus control (3-4 mice/group after accounting for mortality): PBS sham, metoprolol at 30mg/kg/day, empagliflozin at 10mg/kg/day, M-EVs+ metoprolol, and M-EVs + empagliflozin. 1.0x10
9
M-EVs were directly injected into the peri-infarct region via thoracotomy approach shortly after LAD ligation in the applicable groups. Metoprolol and empagliflozin were administered via daily oral gavage. LV function was assessed by cardiac MRI at week 4 after LAD infarct. M-EVs were collected using differential ultracentrifugation of iCM-conditioned medium. Quality and concentrations are determined via nanoparticle analyzer.
Results:
The average LV ejection…
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