Regulation of macrophage migration in ischemic mouse hearts via an AKT2/NBA1/SPK1 pathway
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Yanping Yang1,*, Jieqiong Zhao1,*, Juan Zhang1,*, Yonghong Lei2, Fang Yuan3, Lu Liu4, Haibo Gao1, Hua Guo1, Xiaolin Niu1, Ruirui Chen1, Xiaobing Fu2, Yan Han5, Hua Han6, Tung Chan1, Lianyou Zhao1, Haichang Wang1, Qiangsun Zheng1,7 and Xue Li1
1Cardiovascular Department, Tangdu Hospital, The Fourth Military Medical University, Xian 710038, PR China
2Wound Healing and Cell Biology Laboratory, The First Affiliated Hospital, Chinese PLA General Hospital, Beijing 100853, PR China
3Department of Orthopedics, Chinese PLA General Hospital, Beijing 100853, PR China
4Department of Nutrition, Chinese PLA General Hospital, Beijing 100853, PR China
5Department of Plastic Surgery, Chinese General Hospital, Beijing 100853, PR China
6Department of Molecular Biology, The Fourth Military Medical University, Xian 710038, PR China
7Cardiovascular Department, Xibei Hospital, Xian 710038, PR China
*These authors have contributed equally to this work
Xue Li, email: firstname.lastname@example.org
Qiangsun Zheng, email: email@example.com
Keywords: macrophage migration; atorvastatin; myocardial infarction; cardiac function
Received: June 13, 2017 Accepted: December 01, 2017 Published: December 15, 2017
The role of the AKT2/NBA1/SPK1 signaling cascade in macrophage migration regulation and post-ischemic cardiac remodeling was investigated. We determined that the AKT2/NBA1/SPK1 signaling cascade regulated macrophage migration. A novel role for NBA1 in macrophage migration was discovered. Elevated AKT2 phosphorylation, NBA1, SPK1 (along with phosphorylated SPK1) levels, macrophage recruitment, apoptosis, and fibrosis were found within the infarct area. Atorvastatin had a beneficial effect on cardiac remodeling following myocardial infarction by inhibiting AKT2/NBA1/SPK1-mediated macrophage recruitment, apoptosis, and collagen deposition while increasing angiogenesis in the infarct area. Atorvastatin-related protection of cardiac remodeling following myocardial infarction was abolished in SPK1-KO mice. The AKT2/NAB1/SPK1 pathway is a novel regulating factor of macrophage migration and cardiac remodeling after myocardial infarction.
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