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

Autor: Vincent J. Venditto, Lakshman Chelvarajan, David J. Feola, Dalia Haydar, Ahmed Abdel-Latif, Himi Tripathi, Erhe Gao, John C. Gensel, Ahmed Al-Darraji, Bryana R. Levitan
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Male
Angiogenesis
Physiology
Neutrophils
Myocardial Infarction
lcsh:Medicine
Administration
Oral
Apoptosis
Cardiotonic Agents
Pharmacology
Azithromycin
Pathology and Laboratory Medicine
Monocytes
White Blood Cells
Mice
Animal Cells
Immune Physiology
Medicine and Health Sciences
Myocardial infarction
lcsh:Science
Immune Response
Innate Immune System
Multidisciplinary
Cell Death
Heart
3. Good health
Cell Processes
Absolute neutrophil count
Cytokines
medicine.symptom
Cellular Types
Anatomy
Research Article
Immune Cells
Immunology
Cardiology
Neovascularization
Physiologic
Inflammation
03 medical and health sciences
Signs and Symptoms
Diagnostic Medicine
medicine
Animals
Blood Cells
business.industry
Macrophages
lcsh:R
Biology and Life Sciences
Cell Biology
Hypoxia (medical)
Molecular Development
medicine.disease
Antigens
Differentiation
030104 developmental biology
Heart failure
Immune System
Cardiovascular Anatomy
lcsh:Q
business
Developmental Biology
Zdroj: PLoS ONE
PLoS ONE, Vol 13, Iss 7, p e0200474 (2018)
ISSN: 1932-6203
Popis: Introduction 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. Methods and results 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 changes were associated with a significant decline in pro- and increase in anti-inflammatory cytokines. Mechanistic studies confirmed the ability of AZM to shift macrophage response towards an anti-inflammatory state under hypoxia/reperfusion stress. Additionally, AZM treatment was associated with a distinct decrease in neutrophil count due to apoptosis, a known signal for shifting macrophages towards the anti-inflammatory phenotype. Finally, AZM treatment improved cardiac recovery, scar size, and angiogenesis. Conclusion Azithromycin plays a cardioprotective role in the early phase post-MI through attenuating inflammation and enhancing cardiac recovery. Post-MI treatment and human translational studies are warranted to examine the therapeutic applications of AZM.
Databáze: OpenAIRE
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