AGGF1 protects from myocardial ischemia/reperfusion injury by regulating myocardial apoptosis and angiogenesis

Abstract

Angiogenic factor with G patch and FHA domains 1 (AGGF1) is a newly identified proangiogenic protein, which plays an important role in vascular disease and angiogenesis. However, its role in myocardial ischemia/reperfusion (I/R) injury remains unknown. This study investigated whether AGGF1 is involved in the pathogenesis of mouse myocardial I/R injury and the underlying mechanisms. Wild-type (WT) C57BL/6 J mice were treated at 30 min prior to I/R injury with anti-AGGF1 neutralizing antibody (3 mg/kg) or recombinant human AGGF1 (rhAGGF1, 0.25 mg/kg). After I/R injury, the infarct size, the number of TUNEL-positive cardiomyocytes, Bax/Bcl2 ratio, inflammatory cytokine expression and angiogenesis were markedly increased as compared with sham control. Treatment of WT mice with anti-AGGF1 neutralizing antibody resulted in exaggeration of myocardial I/R injury but reducing angiogenesis. In contrast, administration of rhAGGF1 markedly reversed these effects. Furthermore, anti-AGGF1- or rhAGGF1-mediated effects on I/R-induced cardiac apoptosis, inflammation and angiogenesis were dose dependent. In addition, the protective effects of AGGF1 on cardiomyocyte apoptosis and inflammation were confirmed in cultured cardiomyocytes after I/R. Finally, these effects were associated with activation of ERK1/2, Stat3 and HIF-1α/VEGF pathways and inhibition of activation of NF-κB, p53 and JNK1/2 pathways. In conclusion, we report the first in vivo and in vitro evidence that AGGF1 reduces myocardial apoptosis and inflammation and enhances angiogenesis, leading to decreased infarct size after I/R injury. These results may provide a novel therapeutic approach for ischemic heart diseases.

Overexpression of AGGF1 is correlated with angiogenesis and poor prognosis of hepatocellular carcinoma

“…Enforced expression of AGGF1 enhances angiogenesis and increases the blood flow in ischemic hindlimbs in a mouse model [12]. A recent study has reported that AGGF1 protects from myocardial ischemia/reperfusion injury by reducing myocardial apoptosis and enhancing angiogenesis [17]. In addition to endothelial cells, some types of cancer cells (e.g., bladder urothelial cancer cells [18]) can express AGGF1.…”

The Role of MCPIP1 in Ischemia/Reperfusion Injury-Induced HUVEC Migration and Apoptosis

“…Because the MAPK kinase [1,6] and PI3K/Akt [46] pathways play crucial roles in I/Rmediated signaling, we next examined the involvement of these pathways in the I/R-mediated induction of MCPIP1. First, we examined the effect of I/R on the activation of MAPKs.…”

“…Cardiovascular disease is the leading cause of death in advanced and industrialized countries; ischemia/reperfusion (I/R) injury is an important aspect of cardiovascular disease [1][2][3][4][5]. The prevention and management of I/R injury are key steps in coronary heart disease treatment and are becoming important issues in ischemic heart disease [6,7].…”

Sevoflurane postconditioning protects the myocardium against ischemia/reperfusion injury via activation of the JAK2–STAT3 pathway

“…Some studies showed that myocardial apoptosis is an important aspect of myocardial I/R injury, which has been widely recognized (Huang et al, 2015; Liu et al, 2014; Sodha et al, 2008). Previous investigations indicated that activated JAK2 and STAT3 are sufficient to protect the myocardium against apoptosis (Jiang et al, 2015; Tian et al, 2011).…”