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.

Details

Title
Effects of progranulin on the pathological conditions in experimental myocardial infarction model
Author
Sasaki Takahiro 1 ; Shimazawa Masamitsu 1 ; Kanamori Hiromitsu 2 ; Yamada Yoshihisa 2 ; Nishinaka Anri 1 ; Kuse Yoshiki 1 ; Suzuki Genjiro 3 ; Masuda Tomomi 1 ; Nakamura, Shinsuke 1 ; Hosokawa Masato 3 ; Minatoguchi Shinya 4 ; Hara Hideaki 1 

 Gifu Pharmaceutical University, Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu, Japan (GRID:grid.411697.c) (ISNI:0000 0000 9242 8418) 
 Gifu University Graduate School of Medicine, Department of Cardiology, Gifu, Japan (GRID:grid.256342.4) (ISNI:0000 0004 0370 4927) 
 Tokyo Metropolitan Institute of Medical Science, Dementia Research Project, Department of Dementia and Higher Brain Function, Tokyo, Japan (GRID:grid.272456.0) 
 Gifu University Graduate School of Medicine, Department of Circulatory and Respiratory Advanced Medicine, Gifu, Japan (GRID:grid.256342.4) (ISNI:0000 0004 0370 4927); Gifu Municipal Hospital, Heart Failure Center, Gifu, Japan (GRID:grid.415535.3) 
Publication year
2020
Publication date
2020
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2424342316
Copyright
© The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.