CD47 antibody protects mice from doxorubicin-induced myocardial damage by suppressing cardiomyocyte apoptosis

Exp Ther Med. 2022 May;23(5):350. doi: 10.3892/etm.2022.11277. Epub 2022 Mar 24.ABSTRACTCluster of differentiation 47 (CD47) is upregulated in mouse models of doxorubicin (Dox)-induced dilated cardiomyopathy (DCM). To explore the role of CD47 in the development of DCM, in the present study, CD47 signaling was blocked by an anti-CD47 neutralizing antibody (aCD47) in mice with Dox-induced DCM. Intraperitoneal (i.p.) administration of 10 mg/kg Dox once a week significantly induced the development of DCM after 4 weeks, which was accompanied by the upregulation of CD47 expression in heart tissues. However, co-administration of Dox with 7 mg/kg aCD47 once a week significantly reduced the severity of DCM, with lower numbers of disordered and broken myofibers, reduced cardiomyocytes and infiltration of macrophages in the heart tissues of treated mice. The beneficial effects were associated with the reduced population of Annexin V+7-AAD- apoptotic cells, and the attenuated formation of interstitial fibrosis and release of lactate dehydrogenase (LDH) in the aCD47-treated mice. In addition, co-administration with aCD47 effectively reduced the expression of Bax, collagen I, interleukin (IL)-6 and tumor necrosis factor (TNF)-α in murine DCM. These results were further supported by an in vitro study, in which aCD47 pre-treatment significantly reduced the Dox-induced early apoptosis of cardiomyocytes and suppressed the expression of Bax, cleaved caspase-1/3 and phosphorylation of p38 MAPK....
Source: Experimental and Therapeutic Medicine - Category: General Medicine Authors: Source Type: research