CD47 antibody suppresses isoproterenol-induced cardiac hypertrophy through activation of autophagy.

ABSTRACT: In this study, we investigated whether CD47 antibody could attenuate isoproterenol (ISO)-induced cardiac hypertrophy in mice and H9C2 cells. Cardiac hypertrophy was induced by intraperitoneal (i.p.) injection of ISO (60 mg.kg-1.d-1 in 100 µl of sterile normal saline) daily for 14 days, and cell hypertrophy was induced by ISO (10-5 mol/l) for 48 h. The injury was confirmed by increased levels of lactate dehydrogenase (LDH) and creatine kinase MB (CK-MB), increased heart-to-body weight (HW/BW) ratio and visible cardiac fibrosis. Apoptosis was evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. Autophagic flux in H9c2 cells was monitored by TEM and mRFP-GFP-LC3 virus transfection. The expression levels of Cleaved caspase-3, Cleaved caspase-9 and autophagy-related proteins were detected by Western blotting. CD47 antibody significantly limited ISO-induced increases in LDH, CK-MB, HW/BW ratio and attenuated cardiac fibrosis, oxidative stress, and apoptosis in the heart; CD47 antibody promoted autophagy flow and decreased cell apoptosis in cardiac tissues. Moreover, autophagy inhibitor chloroquine (CQ) reversed the effect of CD47 antibody treatment. In conclusion, CD47 antibody reduced ISO-induced cardiac hypertrophy by improving autophagy flux and rescuing autophagic clearance.

SUBMITTER: Li Y 

PROVIDER: S-EPMC7540123 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature