Effects of progranulin on the pathological conditions in experimental myocardial infarction model

Takahiro Sasaki,Shinya Minatoguchi,Genjiro Suzuki,Shinsuke Nakamura,Hideaki Hara,Yoshihisa Yamada,Masamitsu Shimazawa,Masato Hosokawa,Anri Nishinaka,Yoshiki Kuse,Tomomi Masuda,Hiromitsu Kanamori

doi:10.1038/s41598-020-68804-7

Abstract

Progranulin is a secreted growth factor associated with multiple physiological functions in ischemic pathophysiology. However, it is still not fully understood how progranulin is involved in ischemic lesion and cardiac remodeling after myocardial infarction (MI). In this study, we investigated the effects of progranulin on myocardial ischemia and reperfusion injury. We investigated progranulin expression using Western blotting and immunostaining after permanent left coronary artery (LCA) occlusion in mice. Infarct size and the number of infiltrating neutrophils were measured 24 h after permanent LCA occlusion. Recombinant mouse progranulin was administered before LCA occlusion. In addition, we evaluated cardiac function using cardiac catheterization and echocardiography, and fibrosis size by Masson’s trichrome staining after myocardial ischemia/reperfusion in rabbits. Recombinant human progranulin was administered immediately after induction of reperfusion. Progranulin expression increased in the myocardial ischemic area 1, 3, and 5 days after permanent LCA occlusion in mice. The administration of recombinant mouse progranulin significantly attenuated infarct size and infiltrating neutrophils 24 h after permanent LCA occlusion in mice. We also found that administration of recombinant human progranulin ameliorated the deterioration of cardiac dysfunction and fibrosis after myocardial ischemia/reperfusion in rabbits. These findings suggest that progranulin may protect myocardial ischemia/reperfusion injury.

Highlights

Progranulin is a secreted growth factor associated with multiple physiological functions in ischemic pathophysiology
We investigated the expression of progranulin in ischemic and non-ischemic myocardium 6 h and [1, 3, 5], and 7 days after permanent left coronary artery (LCA) occlusion in mice
We revealed that administration of recombinant progranulin decreased infarct size and infiltrating neutrophils after permanent LCA occlusion in mice, and improved cardiac dysfunction and fibrosis after myocardial I/R in rabbits

Summary

Introduction

Progranulin is a secreted growth factor associated with multiple physiological functions in ischemic pathophysiology It is still not fully understood how progranulin is involved in ischemic lesion and cardiac remodeling after myocardial infarction (MI). The administration of recombinant mouse progranulin significantly attenuated infarct size and infiltrating neutrophils 24 h after permanent LCA occlusion in mice. Enlargement of I/R injury from delayed reperfusion therapy increases the risk of subsequent developments of cardiac rupture and heart failure, in patients with AMI 7. It recently has been reported that progranulin protects cardiac dysfunction in the early phase after myocardial I/R injury 18 It is still not fully understood how progranulin is involved in ischemic lesion and cardiac remodeling after AMI. We investigated the effects of progranulin on ischemic lesion and cardiac remodeling after myocardial I/R and permanent ischemia using experimental animal models of MI

Methods

Results

Conclusion