Cytosolic DNA Sensing Promotes Macrophage Transformation and Governs Myocardial Ischemic Injury

• DOI: 10.1161/circulationaha.117.031046
• Publication Date: 2018-02-01T10:25:17Z
• Authors: Dian J. Cao; Gabriele G. Schia...; Elisa Villalobos; Nan Jiang; Herman I. May; Tuo Li; Zhijian J. Chen; Thomas G. Gillette; Joseph A. Hill
• Keywords: Ventricular remodeling

Myocardium irreversibly injured by ischemic stress must be efficiently repaired to maintain tissue integrity and contractile performance. Macrophages play critical roles in this process. These cells transform across a spectrum of phenotypes accomplish diverse functions ranging from mediating the initial inflammatory responses that clear damaged subsequent reparative help rebuild replacement tissue. Although macrophage transformation is crucial myocardial repair, events governing are poorly understood.Here, we set out determine whether innate immune triggered cytoplasmic DNA role.We report injury, along with resulting release nucleic acids, activates recently described cyclic GMP-AMP synthase-stimulator interferon genes pathway. Animals lacking synthase display significantly improved early survival after infarction diminished pathological remodeling, including ventricular rupture, enhanced angiogenesis, preserved function. Furthermore, loss function abolishes induction key programs such as inducible nitric oxide promotes macrophages phenotype, which results repair hemodynamic performance.These reveal, for first time, cytosolic receptor during cardiac ischemia pattern recognition sterile response. pathway governs transformation, thereby regulating postinjury repair. Because modulators currently clinical use, our findings raise prospect new treatment options combat heart disease its progression failure.