GENETIC MUTATION OF GALECTIN-3 ALTERED THE TEMPORAL EVOLUTION OF MACROPHAGE INFILTRATION AND HEALING AFFECTING THE CARDIAC REMODELING AND FUNCTION AFTER MYOCARDIAL INFARCTION IN MICE

GONZALEZ GERMÁN; CASSAGLIA PABLO; PENAS FEDERICO; MARTINEZ NADIA; BETTAZA CELESTE; WILENSKY LUCIANA; FONTANA ESTEVEZ FLORENCIA SOFÍA; TRUANT SOFIA; MIKSZTOWICZ VERONICA; CEVEY ÁGATA; CICALE ELIANA; BERG GABRIELA; FERNANDEZ MARISA; GOREN NORA BEATRIZ; MORALES CELINA

París

Congreso; ESC Congress 2019; 2019

European Society of Cardiology

Background: Galectin 3 (Gal-3) is a beta-galactoside-binding protein widely expressed in theimmune system. After myocardial infarction, Gal-3 plays an essential role in the regulation ofthe inflammatory response along the natural wound healing evolution. We aimed to study therole of Gal-3 on macrophage polarization, cytokine expression and fibrosis through thetemporal evolution of healing as well as its role in the evolution of remodeling and function.Methods: Adult male C57BL/6J and Gal-3 KO mice were subjected to permanent coronaryligature or sham for 1 and 4 weeks. We studied: 1) mortality; 2) F4/80+ macrophagesinfiltration at the infarct zone by flow cytometry; 3) M1/M2 macrophage polarization bydetection of mannose receptor and YM1 phenotype markers by rt-qPCR; 4) TNF-alpha, IL-6, IL-10 and TGF-beta expression; 5) MMP-2 activity by zymography; 6) fibrosis by histology; 7) LVfunction and remodeling by echocardiography and, 8) myocyte cross-sectional area andcapillary density by immunohistochemistry.Results: At 1 week post-MI, the lack of Gal-3 markedly attenuated F4/80+ macrophageinfiltration at the infarct zone at the same time that substantially increased the expression ofmannose receptor and YM1, markers of M2 macrophages. IL-10, IL-6 and MMP-2 activitywere significantly increased whilst TNF-alpha, TGF-beta and fibrosis were significantly attenuatedat the infarct zone. In Gal-3 KO mice, pulmonary congestion, cardiac remodelling andfunction were severely affected from the beginning of MI as compared to C57 mice. At 4weeks post-MI, the natural evolution of healing in mice lacking Gal-3 was also markedlyaffected since fibrosis was considerably reduced either at the infarct and remote zone whiledilatation remained significantly increased as compared with C57 group.Conclusion: Gal-3 is an essential regulatory factor for the wound healing since it regulatesthe dynamics of the reparative process through the phenotypic profile of macrophages, pro-and anti-inflammatory cytokines expression and fibrosis along the temporal evolution ofmyocardial infarction in mice. The deficit of Gal-3 diminished the infiltration of macrophagesaltering its phenotypic polarization and consequently, the dynamics of the wound healingaggravating the evolution of remodeling and function. New studies should focus on deeplycharacterize the role of Gal-3 on macrophage phenotype infiltrated in heart and itrelationship with chronic remodeling.