The lack of Galectin 3 modifies the evolution of the healing and post‐ myocardial infarct remodeling in mice

Abstract

Myocardial infarction (MI) is a dynamic process that leads to ventricular remodeling (VR) and heart failure (HF). Previous studies established that Galectin‐3 (Gal‐3), is increased during infarction and it is a prognostic marker of HF. Here, we aimed to study the effects of genetic mutation of Gal3 on macrophages infiltration, fibrosis and MMP‐2 as well as VR after MI in mice. Adult male C57 and Gal3KO mice were subjected to permanent coronary artery ligature and sham. After 1 week (w) post‐MI, echocardiography was performed. LV end‐diastolic diameter (LVEDD) was measured and ejection fraction (EF%) calculated. Then, animals were euthanized. Body (BW) and heart weight (HW), tibial length (TL) and lung wet weight (LW) were measured. Hearts were harvested, snap frozen and storage at −80°C. Infarct size and fibrosis in MI area were quantified in cardiac slices stained with Masson's Trichrome and Picrosirius Red. Myocyte cross sectional area (MCSA) was also measured in slices labeled with wheat germ agglutinin–rhodamine. At 1w post‐MI macrophages (F4/80+ cells) were quantified by flow cytometry and MMP‐2 activity was studied by zymography, both in the MI area.Resultsare expressed as X±SEM; * p<0.05 C57 vs Gal3KO. At 1w post‐MI, the pulmonary congestion assessed by the LW/BW ratio (mg/g) was 9 ± 0.4, 8 ± 0.5 and 9 ± 0.4 in C57 sham, Gal3 KO sham and C57 MI, respectively, but it was severely increased to 15 ± 1.2* in the Gal‐3 KO MI. The macrophage infiltration (%) was reduced from 5.6 ± 0.9 to 2.6 ± 0.4 and the fibrosis (%) in infarct zone was reduced from 30 ± 1.0 to 18 ± 0.4* in C57+MI and Gal3KO+MI respectively. At the same time, MMP2 activity increased from 1 ± 0.1 (C57+MI) to 2 ± 0.4*(Gal3KO+MI). The Infarct size (%) increased from 39 ± 5 to 67± 5* in C57+MI and Gal3KO+MI respectively. Moreover, EF (%) was reduced from 47 ± 2 to 38 ± 3*, while the LVEDD was increased from 4.4 ± 0.1 to 4.8 ± 0.2* in C57+MI and Gal3KO+MI respectively. Fibrosis at remote zone as well as the hypertrophy index evaluated through the HW/BW ratio (mg/g) were similar between groups. In summary, Gal‐3 is essential for the early wound healing and VR in mice. The lack of Gal‐3 reduces the infiltration of macrophages and fibrosis while increasing the MMP‐2 activity, the infarct size and expansion, LV dilation and dysfunction. New studies should focus on the role of Gal3 on the macrophage phenotype profiles, cytokine expression and chronic remodeling.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.