Azithromycin therapy reduces cardiac inflammation and mitigates adverse cardiac remodeling after myocardial infarction: Potential therapeutic targets in ischemic heart disease

PloS One
Ahmed Al-DarrajiAhmed Abdel-Latif

Abstract

Acute myocardial infarction (MI) is a primary cause of worldwide morbidity and mortality. Macrophages are fundamental components of post-MI inflammation. Pro-inflammatory macrophages can lead to adverse cardiac remodeling and heart failure while anti-inflammatory/reparative macrophages enhance tissue healing. Shifting the balance between pro-inflammatory and reparative macrophages post-MI is a novel therapeutic strategy. Azithromycin (AZM), a commonly used macrolide antibiotic, polarizes macrophages towards the anti-inflammatory phenotype, as shown in animal and human studies. We hypothesized that AZM modulates post-MI inflammation and improves cardiac recovery. Male WT mice (C57BL/6, 6-8 weeks old) were treated with either oral AZM (160 mg/kg/day) or vehicle (control) starting 3 days prior to MI and continued to day 7 post-MI. We observed a significant reduction in mortality with AZM therapy. AZM-treated mice showed a significant decrease in pro-inflammatory (CD45+/Ly6G-/F4-80+/CD86+) and increase in anti-inflammatory (CD45+/Ly6G-/F4-80+/CD206+) macrophages, decreasing the pro-inflammatory/anti-inflammatory macrophage ratio in the heart and peripheral blood as assessed by flow cytometry and immunohistochemistry. Macrophage cha...Continue Reading

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Citations

Jul 3, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Dalia HaydarDavid J Feola
May 28, 2019·Pediatric Research·Raul Chavez-Valdez
May 1, 2020·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Qianqian GuYu Deng
Sep 3, 2020·American Journal of Physiology. Cell Physiology·Kyle I MentkowskiJennifer K Lang
Oct 6, 2020·Journal of Molecular and Cellular Cardiology·Himi TripathiAhmed Abdel-Latif
Feb 7, 2020·Journal of Neuroscience Methods·Nader El SeblaniGreg A Gerhardt
Mar 2, 2021·Frontiers in Immunology·Vincent J VendittoDavid J Feola
Nov 24, 2020·ACS Applied Bio Materials·Pei-Jung WuBrad J Berron

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Methods Mentioned

BETA
flow cytometry
Confocal Microscopy
Assay
ELISA
PCR

Software Mentioned

Prism
GraphPad
NIH ImageJ
FlowJo
ImageJ

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