AGGF1 protects from myocardial ischemia/reperfusion injury by regulating myocardial apoptosis and angiogenesis
Related Experiment Video
Updated: Apr 28, 2026
Improved Rodent Model of Myocardial Ischemia and Reperfusion Injury
Published on: March 7, 2022
1Department of Pathology, Physiology and Pathophysiology, Beijing AnZhen Hospital the Key Laboratory of Remodeling-Related Cardiovascular Diseases, School of Basic Medical Sciences, Capital Medical University, No.10 Xitoutiao, You An Men, Beijing, 100069, China.
Insights
Angiogenic factor with G patch and FHA domains 1 (AGGF1) protects the heart from ischemia/reperfusion injury by reducing apoptosis and inflammation while promoting angiogenesis. This protein offers a potential new therapy for ischemic heart diseases.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Regenerative Medicine
Background:
- Angiogenic factor with G patch and FHA domains 1 (AGGF1) is a novel proangiogenic protein implicated in vascular diseases.
- The role of AGGF1 in myocardial ischemia/reperfusion (I/R) injury is currently unknown.
- Understanding AGGF1's function in cardiac I/R injury is crucial for developing new therapeutic strategies.
Purpose of the Study:
- To investigate the role of AGGF1 in the pathogenesis of mouse myocardial I/R injury.
- To elucidate the underlying molecular mechanisms by which AGGF1 affects cardiac I/R injury.
- To assess the therapeutic potential of AGGF1 in treating myocardial I/R injury.
Main Methods:
- Wild-type C57BL/6 J mice were subjected to myocardial I/R injury.
- Mice were treated with anti-AGGF1 neutralizing antibody or recombinant human AGGF1 (rhAGGF1) prior to I/R.
- Infarct size, cardiomyocyte apoptosis (TUNEL assay), inflammatory markers, and angiogenesis were assessed.
- Experiments were also conducted on cultured cardiomyocytes.
- Key signaling pathways (ERK1/2, Stat3, HIF-1α/VEGF, NF-κB, p53, JNK1/2) were analyzed.
Main Results:
- Anti-AGGF1 antibody exacerbated myocardial I/R injury, increasing infarct size, apoptosis, and inflammation while reducing angiogenesis.
- rhAGGF1 administration significantly attenuated I/R-induced injury, reducing infarct size and apoptosis, and enhancing angiogenesis.
- AGGF1's effects were dose-dependent and confirmed in vitro.
- AGGF1 modulated the activation of pro-survival (ERK1/2, Stat3, HIF-1α/VEGF) and pro-apoptotic/inflammatory (NF-κB, p53, JNK1/2) pathways.
Conclusions:
- AGGF1 demonstrates significant protective effects against myocardial I/R injury.
- AGGF1 reduces cardiac apoptosis and inflammation and promotes angiogenesis.
- These findings suggest AGGF1 as a promising therapeutic target for ischemic heart diseases.
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.
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