Rab27a deletion impairs the therapeutic potential of endothelial progenitor cells for myocardial infarction.

Abstract

Endothelial progenitor cell (EPC) transplantation has shown advantages in the treatment of myocardial infarction (MI) in animal models and clinical trials through mechanisms of direct intercellular contacts, autocrine, and paracrine. However, the effects of EPC transplantation for MI treatment remain controversial and the underlying mechanisms have not been fully elucidated. Here, we explored the role of Rab27a in the therapeutic potential of EPC transplantation in MI. We found that Rab27a knockout impaired the viability, and reduced the proliferation and tube formation function of ECPs. The recovery of cardiac function and improvement of ventricular remodeling from EPCs transplantation were significantly damaged by Rab27a deletion in vivo. Rab27a deletion inhibited the protein expression of phosphoinositide 3-kinase (PI3K) and cyclin D1 and the phosphorylation levels of Akt and FoxO3a. Therefore, Rab27a knockout suppressed the PI3K-Akt-FoxO3a/cyclin D1 signaling pathway. Furthermore, Rab27a ablation dramatically reduced exosome release in EPCs. These results demonstrated that Rab27a plays an essential role in EPC functions. The elucidation of this mechanism provides novel insights into EPC transplantation as a promising treatment for post-MI injuries.

• Authors: Wenyi Zhou, Xuefei Zheng, Chuanfang Cheng, Guixian Guo, Yun Zhong, Weihua Liu, Kefeng Liu, Yanfang Chen, Shiming Liu, Shaojun Liu
• Journal: Molecular and cellular biochemistry (Mol Cell Biochem) Vol. 476 Issue 2 Pg. 797-807 (Feb 2021) ISSN: 1573-4919 [Electronic] Netherlands
• PMID: 33095380 (Publication Type: Journal Article)

Chemical References

• rab27 GTP-Binding Proteins
• Proto-Oncogene Proteins c-akt
• Rab27a protein, mouse

Topics

• Animals
• Bone Marrow Cells (metabolism, pathology)
• Cells, Cultured
• Disease Models, Animal
• Endothelial Progenitor Cells (pathology, transplantation)
• Exosomes (metabolism)
• Gene Deletion
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Myocardial Infarction (genetics, metabolism, pathology, therapy)
• Phosphatidylinositol 3-Kinases (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Signal Transduction
• Stem Cell Transplantation (methods)
• Ventricular Remodeling
• rab27 GTP-Binding Proteins (deficiency, genetics)