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Cellular repressor of E1A-stimulated genes (CREG) is a secreted glycoprotein maintaining maturation and differentiation of cells and tissues. However, role of CREG in myocardial infarction (MI) and post-infarction ventricular remodeling remains unclear. So we aims to elucidate issue in this study.
A total of 120 male mice were divided into 4 groups including sham group, C57BL/6J group, CREG heterozygote (CREG+/-) group and CREG rescue (reCREG+/+) group (recombinant CREG protein was supplemented by subcutaneously embedded micro-pump). Then MI model was established by ligation of mouse left anterior descending coronary artery. Murine deaths were recorded during 28 days of observation. Left ventricular systolic function was evaluated by small animal echocardiography at day 28. Then all the mice were sacrificed and hearts were collected for paraffin sections and cryosections. Ventricular remodeling was assessed by HE and Masson’s staining. Collagen I and III expression were detected by immunofluorescence staining.
CREG+/- group had the highest mortality rate, while reCREG+/+ group had the lowest mortality rate during 28 days after MI injury. Echocardiography showed significantly decreased left ventricular ejection fraction (LVEF) and fractional shortening (FS) in CREG+/- group and markedly increased LVEF and FS in reCREG+/+ group in contrast to C57BL/6J control group. In addition, Collagen I and III were more abundant in CREG+/- group than control group, indicating aggravated cardiac fibrosis and ventricular remodeling. While Collagen I and III were significantly reduced and cardiac fibrosis as well as ventricular remodeling were greatly improved in reCREG+/+ group.
CREG protein protects mice from MI and post-infarction ventricular remodeling, with might lay foundation for development of novel drugs for treatment of MI.