Abstract 17896: Azithromycin Therapy Reduces Cardiac Inflammation and Mitigates Adverse Cardiac Remodeling After Myocardial Infarction

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Abstract

Introduction and Hypothesis: Acute myocardial infarction (AMI) is a primary cause of worldwide morbidity and mortality. Macrophages are fundamental components of post-AMI inflammation. Pro-inflammatory macrophages (M1-like) can lead to adverse cardiac remodeling and heart failure while anti-inflammatory macrophages (M2-like) enhance tissue healing. Shifting the balance between M1 and M2 macrophages post-AMI is a novel therapeutic strategy. Azithromycin (AZM) polarizes macrophages towards M2-like phenotype in animal and human studies. We hypothesized that using AZM can decrease adverse cardiac remodeling and improve heart function following AMI.

Methods and results: Male mice (C57BL/6, 6-8 weeks old) were treated with AZM orally (160 mg/kg/day) or vehicle starting 3 days prior to MI and continued to day 7 post-AMI. We observed significant reduction in mortality with AZM therapy. AZM-treated mice showed reduction in M1-like (CD45+/Ly6G-/F4-80+/CD86+) and increase in M2-like (CD45+/Ly6G-/F4-80+/CD206+) macrophages leading to significant reduction in the M1/M2 ratio in the heart and peripheral blood (Fig 1A) as assessed by flow cytometry. Macrophage changes were associated with significant reduction in pro-inflammatory and increase in anti-inflammatory cytokine production as assessed by real-time PCR (Fig 1B and 1C). Mechanistically, AZM treatment was associated with increased neutrophil apoptosis, a known signal for shifting macrophages towards an M2-like phenotype. AZM treatment was associated with enhanced cardiac recovery, higher global ejection fraction, lower systolic diameter and smaller scar size at 30 days post-AMI (Fig 1D).

Conclusion: Azithromycin plays a cardioprotective role post-AMI through attenuating inflammation and enhancing cardiac recovery. Long term and human translational studies are planned to examine the therapeutic applications of AZM.

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